Bronchial provocation tests are of value in the evaluation of airway hyperresponsiveness. Nonspecific bronchial challenge (methacholine, mannitol, exercise, etc.) is used when the symptoms, physical examination, and measurements of pulmonary function are unremarkable in the diagnosis of asthma, when a patient is suspected of having occupational asthma or exercise-induced bronchoconstriction (EIB), and when a screening test for asthma or EIB is required for some occupational groups in whom bronchospasm would pose an unacceptable hazard. Methacholine inhalation challenge is most widely used pharmacologic challenge and highly sensitive. For appropriate interpretation of the results of methacholine provocation, it is important to perform the test with the standardized protocol and to recognize that inhalation methods significantly influence the sensitivity of the procedure. Indirect challenges (e.g., mannitol and exercise) correlate with airway inflammation and are more specific but less sensitive for asthma. Indirect provocation tests are used to confirm asthma, to differentiate asthma from other airway diseases, and to evaluate EIB.
Asthma ; Asthma, Occupational ; Bronchial Provocation Tests ; Bronchial Spasm ; Bronchoconstriction ; Diagnosis ; Exercise Test ; Humans ; Inflammation ; Inhalation ; Mannitol ; Mass Screening ; Methacholine Chloride ; Occupational Groups ; Physical Examination

PURPOSE: Dyspnea is not widely utilized as an indicator of asthma provocation despite its universal presentation. We hypothesized that dyspnea severity was proportionate with the lung function decline, methacholine dose-step, and the degree of bronchial hyperresponsiveness (BHR). METHODS: We retrospectively analyzed 73 children's bronchial provocation test data with an assessment of dyspnea at every dose-step. Dyspnea severity was scored using a modified Borg (mBorg) scale. A linear mixed effect analysis was performed to evaluate the relationship between the mBorg scale, the percentage fall in the forced expiratory volume in 1 second (FEV1) (ΔFEV1%), the methacholine dose-step, and the degree of BHR (BHR grade). RESULTS: Subjects were divided into 5 BHR groups based on their last methacholine dose-steps. The mBorg scores did not differ significantly among BHR groups (P=0.596, Kruskal-Wallis test). The linear mixed effect analysis showed that ΔFEV1% was affected by the methacholine dose-step (P < 0.001) and BHR grade (P < 0.001). The mBorg score was affected by the dose-step (P < 0.001) and BHR grade (P=0.019). We developed a model to predict the mBorg score and found that it was affected by the methacholine dose-step and ΔFEV1%, elevating it by a score of 0.039 (χ² [1]=21.06, P < 0.001) and 0.327 (χ² [1]=47.45, P < 0.001), respectively. A significant interaction was observed between the methacholine dose-step and ΔFEV1% (χ² [1]=16.20, P < 0.001). CONCLUSIONS: In asthmatic children, inhaled methacholine, as well as the degree of BHR and lung function decline, may affect dyspnea perception during the bronchial provocation test. If we wish to draw meaningful information from dyspnea perception, we have to consider various complicating factors underlying it.
Asthma* ; Bronchial Provocation Tests ; Bronchoconstriction* ; Child* ; Dyspnea* ; Forced Expiratory Volume ; Humans ; Lung ; Methacholine Chloride* ; Retrospective Studies

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

OBJECTIVE: In severe organophosphate (OP) poisoning, administration of atropine via continuous intravenous infusion is typically considered. To date, there have been no studies on predicting successful atropine discontinuation through plasma cholinesterase (PChE) and serum lactate levels, which are monitored during critical care in severe acute OP poisoning. Therefore, we retrospectively evaluated the usefulness of serum lactate and PChE as predictors of successful discontinuation of atropine infusion. METHODS: This retrospective observational study was performed on consecutive adult patients treated for severe acute OP poisoning between March 2011 and December 2016. We sequentially evaluated serum lactate and PChE levels on emergency department arrival and before a discontinuation trial of atropine infusion. Discontinuation of atropine intravenous infusion was attempted in patients after clearance of respiratory secretions and cessation of bronchoconstriction. Discontinuation of atropine infusion attempts were divided into successful and failed trials. RESULTS: A total of 95 trials were conducted in 62 patients. Serum lactate levels before trials were significantly different between patients with successful and failed trials. The area under the curve for prediction of successful atropine discontinuation using serum lactate levels before trial discontinuation were 0.742 (95% confidence interval, 0.638 to 0.846). PChE level was not significantly different between two groups. CONCLUSION: Serum lactate levels before the discontinuation trial of atropine infusion served to predict successful discontinuation in severe acute OP poisoning.
Adult ; Atropine* ; Bronchoconstriction ; Cholinesterases ; Critical Care ; Emergency Service, Hospital ; Humans ; Infusions, Intravenous ; Lactic Acid* ; Observational Study ; Organophosphate Poisoning* ; Plasma ; Poisoning ; Prognosis ; Retrospective Studies

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: Dyspnea is the cardinal symptom of asthma, but it is difficult to quantify clinically. Although modified Borg (mBorg) scale has been successfully used in adult, but there has been some difficulties to apply in children. Recently, Pediatric Dyspnea Scale (PDS) was adequately designed and has been widely used. The aim of this study is to compare 2 evaluating scales of dyspnea provoked by induced-bronchoconstriction in childhood asthma. METHODS: Seventy-three clinically suspected children with asthma were enrolled in this study. Each ‘fractional exhaled nitric oxide (FeNO)’ was documented. Forced expiratory volume in 1 second (FEV₁), mBorg score and PDS score were recorded during methacholine provocation test. RESULTS: Mapping using canonical plot demonstrated global similarity between 2 scales with some distinctive features. Whereas mBorg score showed more diverse categories in low level of dyspnea, PDS score did in medium level of it. A distribution of dyspnea perception score at a 20% decrease in FEV₁ relative to baseline (PS₂₀), a perception score of dyspnea at 20% fall in FEV1 of 2 scales represented similar wide, biphasic feature. Statistical relevance was verified with spearman correlation (R(s)=0.903, P<0.001) and Bland-Altman analysis. PS₂₀ of both scores and FeNO had no statistical relationship. While relationship between PS20 by mBorg score and the concentration of methacholine at 20% fall in FEV₁ (PC₂₀) was not significant (R(s)=0.224, P=0.154), that between PS₂₀ by PDS and PC₂₀ was weak positive (R(s)=0.29, P=0.063). CONCLUSION: PDS had similar pattern to assess the dyspnea with the mBorg scale suggesting adequacy of PDS in evaluating pediatric clinical asthma. We expect these scales to help clinical practice in complementary ways.
Adult ; Asthma* ; Bronchial Provocation Tests ; Bronchoconstriction* ; Child* ; Dyspnea* ; Forced Expiratory Volume ; Humans ; Methacholine Chloride ; Nitric Oxide ; Weights and Measures

We present a case of a 41-day-old girl with diffuse hemangiomatosis on her chin, right thigh, occipital area, and liver. She also had hepatomegaly, heart failure, and hypothyroidism. Hemangiomatosis did not respond to 2 weeks of oral administration of prednisolone, but was successfully treated with propranolol. After 2 years of propranolol treatment, the lesions of hemangiomatosis nearly disappeared. Hypothyroidism was controlled by levothyroxine replacement. As hemangiomatosis regressed, thyroid function was normalized. Propranolol may have adverse effects including hypotension, hypoglycemia, bronchoconstriction, and restlessness, but she did not experience such adverse effects. Propranolol could be the first choice for diffuse neonatal hemangiomatosis (DNH). Our case also suggests that thyroid function test is needed in patient with DNH.
Administration, Oral ; Bronchoconstriction ; Chin ; Female ; Heart Failure ; Hepatomegaly ; Humans ; Hypoglycemia ; Hypotension ; Hypothyroidism ; Liver ; Prednisolone ; Propranolol ; Psychomotor Agitation ; Thigh ; Thyroid Function Tests ; Thyroid Gland ; Thyroxine

BACKGROUND: Propranolol, a beta-blocker and well known anti-hypertensive medication, has been used as the first-line therapy for pediatric hemangioma since 2010. The objective of this study is to analyze the efficacy and safety of propranolol when used to treat pediatric hemangioma patients for one year or longer in a single institution.METHODS: A retrospective chart review analysis was done of 65 pediatric hemangioma patients treated with oral propranolol as the first-line therapy from 2010 to 2016. The patients were examined regularly at an interval of 1 to 2 months for changes in hemangioma size, growth and development, and occurrence of acute side effects of propranolol such as hypotension, hypoglycemia and bronchial constriction.RESULTS: Twenty patients were treated with propranolol for a year or longer and their median age was 202 days (range, 36 to 4,284 days) and mean duration of treatment was 22.5 months (range, 12 to 49 months). At 12 months of treatment, the average percentage of size decrement was 40.5%. When the weight and height percentile were compared between at diagnosis and 12 months post-treatment, all 20 patients showed normal growth curve and development. Patients did not show any acute side effects of propranolol during 12 months of treatment. One patient experienced hypoglycemia induced seizure, but this event was subsequently diagnosed as ketotic hypoglycemia induced from prolonged fasting.CONCLUSION: Propranolol was effective and well tolerated in children with hemangioma when used for one year or longer.
Bronchoconstriction ; Child ; Diagnosis ; Fasting ; Growth and Development ; Hemangioma ; Humans ; Hypoglycemia ; Hypotension ; Propranolol ; Retrospective Studies ; Seizures

BACKGROUND: The influence of bathing in asthma patients is not yet fully known. OBJECTIVE: We conducted an observational study to investigate changes in symptoms and their degree by bathing in asthmatic patients. METHODS: A questionnaire focusing on ever experienced bathing-induced symptom changes and their degree, as well as contributing factors, was designed and administered to asthmatic patients in the outpatient department of our institute between January 2012 and November 2013. RESULTS: Two hundred fifteen cases were recruited. In 60 cases (27.9%), asthmatic symptoms appeared, including 20 cases of chest discomfort (33.3%), 19 cases of cough (31.7%), and 21 cases of wheezing (35.0%). The triggering factors included vapor inhalation (32 cases, 53.3%), hydrostatic pressure on the thorax due to body immersion in the bathtub (26 cases, 43.3%), and sudden change of air temperature (16 cases, 26.7%). Thirty-eight cases (17.7%) experienced improvement in active asthmatic symptoms by bathing. Vapor inhalation was the most common contributing factor (34 cases, 89.5%), followed by warming of the whole body (13 cases, 34.2%). There was no relationship between asthma severity and the appearance of bathing-induced symptoms or improvement of active asthmatic symptoms by bathing. CONCLUSION: The effects of bathing in asthmatic patients widely differed from patient to patient and their etiology includes several factors. For those who suffer from bathing-induced asthma symptoms, preventive methods, such as premedication with bronchodilators before bathing, should be established. This study is registered in the University Hospital Medical Information Network (UMIN) clinical trials registry in Japan with the registration number UMIN000015641.
Asthma ; Baths ; Bronchoconstriction ; Bronchodilator Agents ; Cough ; Humans ; Hydrostatic Pressure ; Immersion ; Information Services ; Inhalation ; Japan ; Nebulizers and Vaporizers ; Observational Study ; Outpatients ; Premedication ; Respiratory Sounds ; Thorax

PURPOSE: Dysregulated cysteinyl leukotriene (CysLT) synthesis is prominent in exercise-induced bronchoconstriction (EIB). Secreted phospholipase A2 (sPLA2) plays a key regulatory role in the biosynthesis of CysLTs. We previously found that serum leptin levels correlate with (EIB) in children with asthma. The aim of this study was to address the relationship between plasma sPLA2/leptin levels and EIB. METHODS: Sixty-seven prepubertal children between the ages of 6 and 10 years were included in the study. They were asthmatics with EIB (n=25), asthmatics without EIB (n=21), and healthy subjects (n=21). We measured the plasma sPLA2 and leptin levels. We also performed pulmonary function tests at baseline, after bronchodilator inhalation, and after exercise. RESULTS: The sPLA2 and leptin levels were significantly higher in asthmatics with EIB than in those without and control subjects. In addition, sPLA2 levels were significantly correlated with body mass index (Speraman correlation coefficient r=0.343, P=0.023) and leptin levels (partial correlation coefficient r=318, P=0.033). The maximum decrease in % forced expiratory volume in 1 second after exercise was significantly correlated with both PLA2 levels (r=0.301, P=0.041) and leptin levels (r=0.346, P=0.018). CONCLUSION: The sPLA2 and leptin levels were significantly higher in asthmatics with EIB than in asthmatics without EIB and control subjects. In addition, sPLA2 levels were significantly correlated with leptin levels and EIB in asthmatic children.
Asthma ; Body Mass Index ; Bronchoconstriction* ; Child* ; Forced Expiratory Volume ; Humans ; Inhalation ; Leptin* ; Phospholipases A2* ; Plasma* ; Respiratory Function Tests