Clinical analysis of the "small plateau" sign on the flow-volume curve followed by deep learning automated recognition.

BACKGROUND: Small plateau (SP) on the flow-volume curve was found in parts of patients with suspected asthma or upper airway abnormalities, but it lacks clear scientific proof. Therefore, we aimed to characterize its clinical features. METHODS: We involved patients by reviewing the bronchoprovocation test (BPT) and bronchodilator test (BDT) completed between October 2017 and October 2020 to assess the characteristics of the sign. Patients who underwent laryngoscopy were assigned to perform spirometry to analyze the relationship of the sign and upper airway abnormalities. SP-Network was developed to recognition of the sign using flow-volume curves. RESULTS: Of 13,661 BPTs and 8,168 BDTs completed, we labeled 2,123 (15.5%) and 219 (2.7%) patients with the sign, respectively. Among them, there were 1,782 (83.9%) with the negative-BPT and 194 (88.6%) with the negative-BDT. Patients with SP sign had higher median FVC and FEV1% predicted (both P < .0001). Of 48 patients (16 with and 32 without the sign) who performed laryngoscopy and spirometry, the rate of laryngoscopy-diagnosis upper airway abnormalities in patients with the sign (63%) was higher than those without the sign (31%) (P = 0.038). SP-Network achieved an accuracy of 95.2% in the task of automatic recognition of the sign. CONCLUSIONS: SP sign is featured on the flow-volume curve and recognized by the SP-Network model. Patients with the sign are less likely to have airway hyperresponsiveness, automatic visualizing of this sign is helpful for primary care centers where BPT cannot available.

Evaluation of bronchial challenge test results for use in assessment of paediatric eczema: a retrospective series.

BACKGROUND: Atopic dermatitis (AD), asthma, and allergic rhinitis are associated diseases involved in the atopic march. The bronchial challenge test (BCT) is a tool that evaluates airway hyperresponsiveness in patients with asthma. This study aimed to evaluate whether a positive BCT result is useful in assessment of paediatric AD. METHODS: This retrospective case series included 284 patients with AD who had BCT results. Clinical information and laboratory parameters were reviewed, including AD severity (using the SCORing Atopic Dermatitis [SCORAD]), skin hydration, and transepidermal water loss. RESULTS: Of the 284 patients who had BCT, 106 had positive BCT results and 178 had negative BCT results. A positive BCT result was associated with a history of asthma (P<0.0005), sibling with asthma (P=0.048), serum immunoglobulin E (P=0.045), eosinophil count (P=0.017), and sensitisation to food allergens in the skin prick test (P=0.027). There was no association between a positive BCT result and personal allergic rhinitis, parental atopy, sibling allergic rhinitis or AD, skin prick response to dust mites, objective SCORAD score, skin hydration, transepidermal water loss, exposure to smoking, incense burning, cat or dog ownership, or AD treatment aspects (eg, food avoidance and traditional Chinese medicine). Logistic regression showed significant associations of a positive BCT result with a history of asthma (adjusted odds ratio=4.05; 95% confidence interval=1.92-8.55; P<0.0005) and sibling atopy (adjusted odds ratio=2.25; 95% confidence interval=1.03-4.92; P=0.042). CONCLUSIONS: In patients with paediatric AD, a positive BCT result was independently and positively associated with personal history of asthma and sibling history of atopy, but not with any other clinical parameters.

Identification of late asthmatic reactions following specific inhalation challenge.

Specific inhalation challenge (SIC) is the reference standard for the diagnosis of occupational asthma. Current guidelines for identifying late asthmatic reactions are not evidence based. OBJECTIVES: To identify the fall in forced expiratory volume in 1 s (FEV1) required following SIC to exceed the 95% CI for control days, factors which influence this and to show how this can be applied in routine practice using a statistical method based on the pooled SD for FEV1 from three control days. METHODS: Fifty consecutive workers being investigated for occupational asthma were asked to self-record FEV1 hourly for 2 days before admission for SIC. These 2 days were added to the in-hospital control day to calculate the pooled SD and 95% CI. RESULTS: 45/50 kept adequate measurements. The pooled 95% CI was 385 mL (SD 126), or 14.2% (SD 6.2) of the baseline FEV1, but was unrelated to the baseline FEV1 (r=0.06, p=0.68), or gender, atopy, smoking, non-specific reactivity or treatment before or during SIC. Thirteen workers had a late asthmatic reaction with ≥2 consecutive FEV1 measurements below the 95% CI for pooled control days, 4/13 had <15% and 9/13 >15% late fall from baseline. The four workers with ≥2 values below the 95% CI all had independent evidence of occupational asthma. CONCLUSION: The pooled SD method for defining late asthmatic reactions has scientific validity, accounts for interpatient spirometric variability and diurnal variation and can identify clinically relevant late asthmatic reactions from smaller exposures. For baseline FEV1 <2.5 L, a 15% fall is within the 95% CI.

Hyperpolarized Helium 3 MRI in Mild-to-Moderate Asthma: Prediction of Postbronchodilator Reversibility.

Background Longitudinal progression to irreversible airflow limitation occurs in approximately 10% of patients with asthma, but it is difficult to identify patients who are at risk for this transition. Purpose To investigate 6-year longitudinal changes in hyperpolarized helium 3 (3He) MRI ventilation defects in study participants with mild-to-moderate asthma and identify predictors of longitudinal changes in postbronchodilator forced expiratory volume in 1 second (FEV1) reversibility Materials and Methods Spirometry and hyperpolarized 3He MRI were evaluated in participants with mild-to-moderate asthma in two prospectively planned visits approximately 6 years apart. Participants underwent methacholine challenge at baseline (January 2010 to April 2011) and pre- and postbronchodilator evaluations at follow-up (November 2016 to June 2017). FEV1 and MRI ventilation defects, quantified as ventilation defect volume (VDV), were compared between visits by using paired t tests. Participants were dichotomized by postbronchodilator change in FEV1 at follow-up, and differences between reversible and not-reversible groups were determined by using unpaired t tests. Multivariable models were generated to explain postbronchodilator FEV1 reversibility at follow-up. Results Eleven participants with asthma (mean age, 42 years ± 9 [standard deviation]; seven men) were evaluated at baseline and after mean 78 months ± 7. Medications, exacerbations, FEV1 (76% predicted vs 76% predicted; P = .91), and VDV (240 mL vs 250 mL; P = .92) were not different between visits. In eight of 11 participants (73%), MRI ventilation defects at baseline were at the same location in the lung at follow-up MRI. In the remaining three participants (27%), MRI ventilation defects worsened at the same lung locations as depicted at baseline methacholine-induced ventilation. At follow-up, postbronchodilator FEV1 was not reversible in six of 11 participants; the concentration of methacholine to decrease FEV1 by 20% (PC20) was greater in FEV1-irreversible participants at follow-up (P = .01). In a multivariable model, baseline MRI VDV helped to predict postbronchodilator reversibility at follow-up (R 2 = 0.80; P < .01), but PC20, age, and FEV1 did not (R 2 = 0.63; P = .15). Conclusion MRI-derived, spatially persistent ventilation defects predict postbronchodilator reversibility 78 months ± 7 later for participants with mild-to-moderate asthma in whom there were no changes in lung function, medication, or exacerbations. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Stojanovska in this issue.

Changes in fractional exhaled nitric oxide levels after bronchial challenge with Aspirin in patients with Aspirin-induced asthma

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Chlorine Inhalation Challenge in Humans: Development of a New Closed-Circuit Methodology / Prueba de provocación bronquial con cloro en humanos: desarrollo de una nueva metodología con circuito-cerrado

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[Occurrence of delayed symptoms after a challenge test with methacholine]. / Survenue de symptômes tardifs après un test de provocation par la méthacholine.

There are few prospective studies available on the development of delayed symptoms following challenge tests with methacholine (MCT) at the currently recommended doses. The objective of this study was to describe the nature and frequency of respiratory symptoms suggestive of bronchospasm developing within 24hours after a MCT. The study was offered to adult patients who underwent MCT seen consecutively between June and October 2015. Following the test, a questionnaire adapted from the GINA asthma control questionnaire bearing on diurnal and nocturnal symptoms (cough, dyspnoea, wheeze and tightness), was delivered to the patient and the replies collected by telephone 24hours later. Of the 101 patients included (initial FEV1 2.82±0.79L), 46 (46 %) were MCT+ and 55 (54 %) MCT-. Among the MCT-, 4 (7 %) presented with immediate symptoms (S+) and 4 (7 %) with delayed symptoms. Among the MCT+ patients, 36 (78 %) presented with immediate symptoms (P<0.001 compared with the MCT- patients), and 39 (85 %) with delayed symptoms (P<0.001 compared with the MCT- patients). Delayed symptoms developed with a mean of 5h30 after the provocation test. Immediate and delayed symptoms were more frequent in subjects having significant non-specific bronchial hyper-reactivity. Informing patients of the risk of developing delayed symptoms seems useful and allows optimization of their management after a MCT.

Patterns of sensitization to inhalant and food allergens among pediatric patients from the Moscow region (Russian Federation).

The immunological profiles of human specific IgE (sIgE) and specific IgG4 (sIgG4) vary by genetic predisposition, living conditions in different geographical locations and patient's age. The aim of our study was to analyze sIgE and sIgG4 patterns and their age-dependent changes in patients from the Moscow region. For identifying sIgE and sIgG4 profiles the blood samples from 513 patients aged 6 months to 17 years who were showing symptoms of allergic diseases were analyzed using microarrays containing 31 allergens. The highest sIgE prevalence was observed for birch pollen (32%) among pollen allergens, cat dander (24%) among indoor allergens, and egg whites (21%) among food allergens. The most common sIgG4 response was developed toward egg whites (80% of patients). Age-related elevation was identified for patients with increased sIgE to pollen allergens and indoor allergens (cat or dog dander and house dust mites). For each allergen, the proportion of cases with significant levels of sIgG4 appeared to increase with patients' age. The data on allergen-specific sIgE and sIgG4 prevalence show both general trends and some local special aspects that are indicative for the Moscow region. This information should be useful in terms of epidemiology of allergic diseases.

Detection of smoothly distributed spatial outliers, with applications to identifying the distribution of parenchymal hyperinflation following an airway challenge in asthmatics.

Methacholine challenge tests are used to measure changes in pulmonary function that indicate symptoms of asthma. In addition to pulmonary function tests, which measure global changes in pulmonary function, computed tomography images taken at full inspiration before and after administration of methacholine provide local air volume changes (hyper-inflation post methacholine) at individual acinar units, indicating local airway hyperresponsiveness. Some of the acini may have extreme air volume changes relative to the global average, indicating hyperresponsiveness, and those extreme values may occur in clusters. We propose a Gaussian mixture model with a spatial smoothness penalty to improve prediction of hyperresponsive locations that occur in spatial clusters. A simulation study provides evidence that the spatial smoothness penalty improves prediction under different data-generating mechanisms. We apply this method to computed tomography data from Seoul National University Hospital on five healthy and ten asthmatic subjects. Copyright © 2017 John Wiley & Sons, Ltd.

Variability of methacholine bronchoprovocation and the effect of inhaled corticosteroids in mild asthma.

BACKGROUND: The methacholine challenge test quantifies airway hyper-responsiveness, which is measured by the provocative concentration of methacholine causing a 20% decrease in forced expiration volume in 1 second (PC20). The dose-response effect of inhaled corticosteroids (ICS) on PC20 has been inconsistent and within-patient variability of PC20 is not well established. OBJECTIVE: To determine the effect of high- vs low-dose ICS on PC20 and within-patient variability in those with repeated measurements of PC20. METHODS: A randomized, double-masked, crossover trial was conducted in patients with asthma on controller medications with PC20 of 8 mg/mL or lower (n = 64) to evaluate the effect of high-dose (1,000 µg/d) vs low-dose (250 µg/d) fluticasone for 4 weeks on PC20. In addition, the variability of PC20 was assessed in participants who underwent 2 or 3 PC20 measurements on the same dose of ICS (n = 27) over a 4-week interval. RESULTS: Because there was a significant period effect, dose comparison of the change in PC20 was assessed in the first treatment period. There was no significant difference in the change in PC20 for high- vs low-dose ICS (39% vs 30% increase, respectively; P = .87). The within- and between-participant variances for log PC20 were 0.84 and 0.96, respectively, with an intra-class correlation of 0.53, and 37% of participants had more than 2 doubling dose changes in PC20 in those with repeated measurements. CONCLUSION: The effect of ICS on PC20 is not dose dependent at fluticasone levels of 250 and 1,000 µg/d. Interpersonal variability for PC20 is large. A lack of precise measurements should be taken into account when interpreting any change in PC20.

Survey about the use of lung function testing in public hospitals in Catalonia in 2009.

BACKGROUND: Underdiagnosis is one of the problems with the greatest impact on respiratory disease management and requires specific interventions. Access to quality spirometry is especially important and is an objective of the Master Plan for Respiratory Diseases of the Department of Health of the Generalitat de Catalunya. OBJECTIVE: To determine the current use of spirometry at public hospitals in Catalonia, possible deficiencies and options for improvement. METHODS: A cross-sectional survey of 65 public hospitals in Catalonia in 2009. Descriptive analyses were developed for each public health-care region. RESULTS: A lack of uniformity was observed in the use of spirometry at the regional level (between 0,98 and 1.50 spirometries per 100 inhabitants). We identified two factors associated with a higher rate of spirometry: i) the existence of a Respiratory Medicine Department at the hospital, and ii) the existence of a set location to carry out spirometries. Several areas for improvement also were identified: quality control of the test itself, the inclusion of spirometry in electronic health-care records and continuing education programs. CONCLUSIONS: The results of this study have identified areas for improvement in spirometry programs.

Bronchodilation test in patients with allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) may be considered a risk factor for the onset of asthma. Recently, it has been reported that forced expiratory flow between 25% and 75% of vital capacity (FEF25₋75) may predict a positive response to bronchodilation test in asthmatic children. The aim of this study was to evaluate a large group of adult AR patients to investigate the frequency of response to bronchodilation test and FEF25₋75 values. METHODS: One thousand four hundred and sixty-nine consecutive patients suffering from persistent AR were evaluated. Clinical examination, spirometry, and bronchodilation test were performed in all patients. RESULTS: In this study, 62.9% of patients had reversibility to bronchodilation test and 17.8% had impaired FEF25₋75 values (≤ 65% of predicted). Impaired FEF25₋75 values associated with longer rhinitis duration may predict reversibility to bronchodilation test (OR = 11.3; P < 0.001). In addition, a FEF25₋75 cutoff value ≤ 71% of predicted may already discriminate patients with reversibility. CONCLUSIONS: This study highlights that about two-thirds of patients with persistent AR may be considered at risk of becoming asthmatic. This finding should be adequately considered as a precocious spirometry may allow the early detection of patients prone to develop asthma and consequently to treat them.

Diagnosing asthma in children: what is the role for methacholine bronchoprovocation testing?

OBJECTIVE: To determine whether measurement of airways responsiveness to methacholine can help physicians diagnose asthma in children. METHODS: Children from the 1995 Manitoba birth cohort were assessed by asthma specialists, had skin testing and measurement of airways responsiveness to methacholine (PC20). We selected children with doctor-diagnosed asthma and healthy children as controls (no asthma, no allergic rhinitis, negative skin tests). Sensitivities and specificities for asthma were calculated. Receiver operating curves were calculated to determine the best fit of the methacholine challenge as a diagnostic test. RESULTS: 640 children were assessed. Two hundred fifteen children with doctor diagnosed asthma and 197 healthy controls successfully completed a methacholine challenge. Airways hyperresponsiveness was a moderately sensitive and specific measure for the diagnosis of asthma in girls, whether atopic (sensitivity of 71% and specificity of 69% at PC20 < or = 4.0 mg/ml) or not (sensitivity of 77% and specificity of 53% at PC20 < or =8.0 mg/ml). Airways hyperresponsiveness was also helpful for the diagnosis of asthma in atopic boys (sensitivity of 67% and specificity of 75% at PC20 < or =2.0 mg/ml), but of absolutely no help in the diagnosis of asthma in nonatopic boys. CONCLUSION: Measurement of airways hyperresponsiveness to methacholine can be useful in children who are atopic and of some value in nonatopic girls. The presence or absence of airways hyperresponsiveness to methacholine is of no help for the diagnosis of asthma in nonatopic boys. Laboratory tests must be placed in context of the clinical assessment of children for asthma.

Effect of aging on the relationship between asthma severity and bronchial hyperresponsiveness in children with asthma.

An association between asthma and bronchial hyperresponsiveness (BHR) has been demonstrated. It is possible that the relationship between asthma severity and BHR in children with asthma is different in infants and in adolescents. The aim of this study is therefore to evaluate the effect of aging on the relationship between the severity of asthma and BHR in children with asthma. We measured BHR in 386 subjects ranging from 2 to 20 years of age. The subjects consisted of 323 children with asthma (boys:girls = 193:130, mean age 9.7 years) and 63 age-matched controls (boys:girls = 25:38, mean age 8.2 years). BHR was measured using the methacholine inhalation challenge by measuring the transcutaneous oxygen pressure (tcPO2) in children less than 6 years of age (Dmin-PO2) and by measuring the respiratory resistance (Rrs) in children 6 years of age and older (Dmin-Rrs). Throughout the whole age range, both the Dmin-PO2 and Dmin-Rrs in each asthma severity group were higher than those in the controls. In the asthmatics aged 2-5 years, the Dmin-PO2 levels in the mild asthma group were higher than those in the moderate and severe asthma groups (p < 0.001, p < 0.001, respectively), and the Dmin-PO2 levels in the moderate asthma group were also higher than those in the severe asthma group. This tendency was also found in the age ranges of 6-9 years and 10-13 years. In the asthmatics aged 14-20 years, the Dmin-Rrs levels were not significantly different among the three groups. Taken together, these data show that aging has an effect on the relationship between the severity of asthma and BHR during childhood and that BHR may not be the sole determinant for the severity of asthma in adolescence.