Positive Methacholine Challenge Test Research Articles

Standard technical specifications for methacholine chloride (Methacholine) bronchial challenge test (2023)

Standard technical specifications for methacholine chloride (Methacholine) bronchial challenge test (2023)

Pulmonary Function Tests in Thunderstorm-associated Respiratory Symptoms: A Cross-sectional Study.

Epidemic thunderstorm asthma is an observed increase in cases of acute bronchospasm following thunderstorms. This study aimed to compare the frequency of obstructive airway disease or bronchial hyperresponsiveness in subjects with thunderstorm-associated respiratory symptoms with subjects with similar symptoms presented at other times. A cross-sectional study from June to November of 2013 was conducted on subjects with thunderstorm-associated respiratory symptoms living in Ahvaz City, Iran. Thunderstorm-associated subjects were presented with asthmatic symptoms in thunderstorms, and other patients presented with similar symptoms at other times. Baseline spirometry was performed on patients to examine the presence of obstructive airway disease. In all patients with normal spirometry, a provocation test was applied. A comparison of qualitative and quantitative variables was made using the Chi-square and independent t test, respectively. All analyses were carried out using SPSS Statistics Version 22. A P value less than 0.05 was considered statistically significant. Out of 584 subjects, 300 and 284 participants were in thunderstorm-associated and non-thunderstorm-associated groups, respectively. After the final analysis, 87 (30.6%) and 89 (33.3%) of the thunderstorm-associated subjects and non-thunderstorm-associated group, respectively, had pieces of evidence of airflow limitation (P=0.27). Among the patients with normal spirometry, 161 (81.72%) of the thunderstorm-associated patients and 100 (56.17%) patients of the non-thunderstorm-associated symptoms group had a positive methacholine challenge test result (P<0.001). Most of the patients with thunderstorm-associated respiratory symptoms had no obvious evidence of airflow limitation in spirometry.

Association between the Consumption of Ultra-Processed Foods and Asthma in Adults from Ribeirão Preto, São Paulo, Brazil.

Ultra-processed Food (UPF) consumption can play a role in the pathogenesis and progression of asthma. The aim of this study was to evaluate the association between the consumption of UPF and asthma. This cross-sectional study included 1857 adults aged 23-25 years from the Ribeirão Preto-SP birth cohort (1978/1979). The exposure variable was the consumption of UPF (expressed as their percentage contribution to energy intake-% total caloric value [%TCV] and their percentage contribution to the amount of food ingested-%grams), which was assessed with a food frequency questionnaire. Asthma was the outcome and was defined based on a positive methacholine challenge test and the presence of wheezing, chest tightness, or shortness of breath over the last 12 months. Poisson regression with robust variance was used to estimate the association between these variables. Unadjusted analyses and analyses adjusted for sex, age, household income, smoking, and physical activity level were performed. The prevalence of asthma in the sample was 13.2%. The mean total consumption of UPF was 37.9 ± 11.2% TCV (corresponding to 35.1 ± 15.1% grams). There was no association between the consumption of UPF and asthma in adults. This study provides no evidence for an association between the consumption of UPF and asthma in young adults.

Based on what parameters is safe to discontinuate inhaled corticosteroids in children with asthma?

Objective Remission of childhood asthma has not been widely studied. Patients in clinical remission continue to have some degree of bronchial hyperresponsiveness (BHR). The aim of this study was to investigate whether clinical parameters and lung function test are good parameters for discontinuation of inhaled corticosteroids (ICS) in asthmatic children, including patients with persistent BHR, as measured by the methacholine challenge test (MCT). Methods One year after discontinuation of inhaled corticosteroids (ICS), MCT was performed in a group of 40 asthmatic children to confirm or exclude BHR. In all patients, ICS treatment was discontinued based on the same parameters: symptoms, spirometry, daily PEF, and negative bronchodilator test. After achieving complete asthma control for at least 6 to 12 months, ICS treatment was stepped down and discontinued. Clinical course and spirometry were followed up after ICS discontinuation. Results Positive MCT was found in 50% of the patients. There was no statistically significant difference between the positive and negative MCT groups in age at initiation and discontinuation of ICS therapy, duration of ICS therapy, duration of stepping down period, FEV1, and PEF at the time of withdrawal of ICS and one year later. ICS treatment had to be restarted in two patients from the positive MCT group, due to recurrence of asthma symptoms. Conclusion Clinical parameters, normal spirometry, daily PEF values, and a negative bronchodilator test are good parameters for discontinuing ICS treatment in asthmatic children, even in patients with persistent BHR. Children should continue to be monitored, as symptoms may recur.

Methacholine and FeNO Measurement in Patients with Habit Cough.

Chronic cough is one of the most common symptoms in childhood. Making a definite diagnosis is a challenge for all pediatricians especially in patients when cough is without an organic cause like in habit cough. In this retrospective analysis, all electronic outpatient charts of the Division of Allergology and Pneumology, between January 1, 2010 and December 31, 2019 were reviewed in order to study all children with potential habit cough. All children underwent the following diagnostic algorithms, skin prick test (SPT), measurement of fractional exhaled nitric oxide (FeNO), spirometry and methacholine challenge test (MCT). The value of a normal MCT and FeNO measurement for diagnosing habit cough was investigated. The chart review revealed 482 patients with chronic cough>4 weeks. Of these, 99 (20.5%) with suspected habit cough were collected. 13 patients had to be excluded for other diagnosis and a complete data set was available in 55 patients. 33 (60.0%) of 55 patients were SPT negative and 22 (40.0%) had sensitization to common allergens. Five patients had elevated FeNO≥20 ppb and three showed severe bronchial hyperresponsiveness<0.1 mg methacholine, challenging the diagnosis of habit cough. A normal FeNO and MCT can help confirm the clinical diagnosis of habit cough. However, in patients with positive MCT and/or elevated FeNO habit cough can be present. Especially in patients with elevated FeNO and severe BHR cough variant asthma and eosinophilic bronchitis have to be ruled out.

Sex differences of small airway function and fractional exhaled nitric oxide in patients with mild asthma

BackgroundSex differences of small airway function (SAF) and fractional exhaled nitric oxide (FeNO) in patients with mild asthma remain unclear. ObjectiveTo evaluate sex differences of SAF and FeNO in patients with mild asthma confirmed by positive methacholine challenge test (MCT) result. MethodsThis cross-sectional, double-centered, observational study enrolled 1609 adult patients with forced expiratory volume in 1 second greater than or equal to 80% and suspected asthma symptoms. Data of spirometry, FeNO, impulse oscillometry measurements, and peripheral blood test result were compared between males and females. The receiver-operating characteristic curves of SAF parameters and FeNO in predicting positive MCT result were also calculated. ResultsIn patients with mild asthma matched by age, males had better SAF but higher FeNO levels than females (60 [29.27%] vs 187 [46.75%] for small airway dysfunction, 78.6% vs 72.0% for forced expiratory flow [FEF]50%, 67.5% vs 60.1% for FEF75%, 73.7% vs 67.4% for FEF25%-75%, and 42.0 ppb vs 29.0 ppb for FeNO, respectively, all P ≤ .001). The FeNO levels in male current smokers were considerably lower than those of nonsmokers. SAF and FeNO values declined more rapidly with age among female than male patients with asthma. The optimal cutoff values of FEF25%-75%, FEF50%, and FeNO for predicting a positive MCT result were 81.5%, 86.4%, and 41.0 ppb in males vs 73.7%, 76.9%, and 35.0 ppb in females. ConclusionIn patients with mild asthma, the female patients have worse SAF, lower FeNO levels, and a more prominent decline trend of those parameters with age than males. Sex-specific cutoff values should be considered when SAF parameters (FEF25%-75%, FEF50%), alone or combined with FeNO, are used to predict positive MCT result in asthma diagnosis.

Association of Asthma with COVID-19 Disease Severity in Pediatric Patients

Background: The impact of COVID-19 on asthmatic patients is still uncertain. Objective: This study intended to examine the associations between the severity of coronavirus dis-ease 2019 (COVID-19), asthma, and some inflammatory markers among pediatric patients. Methods: A retrospective study enrolled pediatric COVID-19 patients who were admitted to Abuzar Hospital (Ahvaz, Iran) during eight months. The diagnosis of COVID-19 was according to the real-time reverse transcription-polymerase chain reaction (RT‐PCR) method. Asthma diagnosis was confirmed by specialists through functional and clinical evaluations (positive bronchodilator reversibility test or positive methacholine challenge test). Demographic and clinical characteristics of the patients were documented. Asthmatic patients with COVID-19 were considered as Group 1 (n= 52) and non-asthmatic COVID-19 patients were assigned as Group 2 (n= 54). Results: The mean age of 106 patients was 71.28 ± 50.09 months (range: 1-16 years). Children with severe and moderate COVID-19 had significantly lower levels of neutrophils and lymphocytes, higher inflammatory markers, and longer hospital length of stay (LOS) than patients with a mild course of COVID-19 (p &lt; 0.001). Patients in Group 1 had significantly longer LOS, higher dry cough, chest radiographic findings, fever, levels of D-dimer, fibrinogen, and C-reactive protein (CRP), as well as lower neutrophil and lymphocyte counts, compared with those in Group 2 (p &lt; 0.001). Conclusion: The presence of asthma in COVID-19 patients was associated with severe COVID-19 in comparison with their non-asthmatic counterparts. Additional studies with large sample sizes are deemed necessary to determine the impact of asthma on the management and incidence of COVID-19 disease.

Baseline Spirometry as a Predictor of Positive Methacholine Challenge Testing for Exertional Dyspnea.

There are several tests recommended by the American Thoracic Society (ATS) to evaluate for airway hyper-responsiveness (AHR), one of which is methacholine challenge testing (MCT). Few studies have examined the correlation of baseline spirometry to predict AHR in MCT, especially in the younger, relatively healthy military population under clinical evaluation for symptoms of exertional dyspnea. The study aim was to retrospectively correlate baseline spirometry values with MCT responsiveness. This study is a retrospective review of all MCT performed at Brooke Army Medical Center/Wilford Hall Medical Center over a 12-y period; all completed studies were obtained from electronic databases. The following parameters were analyzed from the studies: baseline FEV1, FVC, FEV1/FVC, mid-expiratory flow (FEV25-75%), FEV25-75%/FVC. Studies were categorized based on baseline obstruction, restriction, FEF25-75% lower limit of normal, and response to bronchodilator testing (if completed); these values were compared based on methacholine reactivity and severity. Methacholine challenge studies (n = 1,933) were reviewed and categorized into reactive (n = 577) and nonreactive (n = 1,356) as determined by ATS guidelines. The mean baseline FEV1 (% predicted) with MCT reactivity was 88.0 ± 13.0% versus no MCT reactivity was 92.7 ± 13.0% (P < .001). The mean baseline FVC (% predicted) was 93.1 ± 13.7% versus 95.3 ± 13.5% (P < .001). The mean baseline FEV25-75% (% predicted) was 80.0 ± 22.1% versus 89.0 ± 23.4% (P < .001). Based on partition analysis, methacholine reactivity was most prevalent with baseline obstruction, n = 115 (43%), and in the absence of obstruction, when the FEF25-75% (% predicted) was below 0.70, n = 111 (40%). The negative predictive value with normal spirometry was 73%. The analysis of baseline spirometry prior to MCT proved useful in the evaluation of exertional dyspnea in a military population. The presence of airways obstruction (FEV1/FVC < lower limit of the normal range) followed by a reduction in FEV25-75% < 70% predicted showed a positive correlation with underlying AHR. In patients with exertional dyspnea and normal baseline spirometry, the use of the FEF25-75% may be a useful surrogate measurement to predict reactivity during MCT and consideration for additional testing or treatment.

Correlation between Reduced FEF25-75% and a Positive Methacholine Challenge Test in Adults with Nonobstructive Baseline Spirometry.

Objective To clarify whether in adults with a nonobstructive spirometry a reduced FEF25-75% is associated with a positive methacholine challenge test (MCT). Methods Data was collected for all the patients who had a MCT done between April 2014 and January 2020 but had nonobstructive baseline spirometry. Logistic regression was utilized to estimate the log odds of a positive methacholine test as a function of FEF25-75% and also for age, gender, BMI, FEV1, and FEV1/FVC. Results Out of 496 patients, 187 (38%) had a positive MCT. Baseline characteristics in two groups were similar except that patients with positive MCT were younger (32 ± 11.57 vs. 38 ± 13.25 years, respectively, p < 0.001). Mean FEF25-75% was lower in MCT positive (3.12 ± 0.99 L/s) vs. MCT negative (3.39 ± 0.97 L/s) patients, p = 0.003. Logistic regression results suggest that MCT outcome is inversely related to FEF25-75%, age, and gender. Specifically, as FEF25-75% percentage of predicted value increases, the log odds of a positive MCT decrease (odds ratio (OR) = 0.90, 95% confidence intervals (CI) = 0.84‐0.96, p = 0.002). Also, as age increases, the log odds of a positive MCT decrease (OR = 0.95, 95%CI = 0.94‐0.97, p < 0.001). Conclusions Reduced FEF25-75% in adults with nonobstructive spirometry can predict a positive response to MCT in younger patients. However, this relationship becomes weaker with increasing age.

90 Lung ultrasound in pediatric asthma patients: A pilot study characterizing findings at baseline stat

Abstract Primary Subject area Emergency Medicine - Paediatric Background Unlike the lung ultrasound (LU) findings of pneumonia, bronchiolitis, pleural effusions and pneumothorax, which have all been well described, the sonographic pattern of asthma remains unclear. Previous pediatric studies have shown that pediatric patients with acute asthma exacerbations had positive LU findings. It is also unclear whether these findings were the result of acute infections associated with the exacerbation or if the findings would be present at baseline, outside an exacerbation in an asthmatic patient. Objectives The primary objective of this study is to characterize lung ultrasound (LU) findings in stable asthma pediatric patients presenting in a tertiary care asthma or respiratory clinic. Design/Methods Eligible patients &amp;gt;6 years of age, underwent a LU by the study sonographer between December 19, 2017 to June 25, 2019, during their regular follow up visit at the pulmonology clinic or scheduled pulmonary function test. Patients were defined as asthmatic if they had a positive methacholine challenge test (MCT) or spirometry at the day of the visit or in the past. Patients were excluded if they had an upper respiratory tract infection in the past 4 weeks, or had any other known pulmonary diseases. Baseline demographic and asthma severity (ISAAC score, ACQ-7) questionnaires were filled out by the patients, following which they underwent a LU by a novice sonographer using a 6-zone protocol. A blinded expert sonographer interpreted the images offline. A positive LU was defined as presence of more than 3 B-lines, consolidation (&amp;lt;1cm or &amp;gt;1cm), absent lung slide, and/or presence of pleural fluid. Results Fifty-two patients were enrolled in the study and 19.2% (CI 8.31-30.15) of the asthma patients had positive LU findings. The positive LU findings were diverse including B-lines (80%), small consolidation (80%), pleural line anomalies (10%). Positive LU findings were not correlated to any demographic value. Conclusion In our study, 19.2% of asthma patients at baseline have a positive LU. Lung consolidations larger than 1 cm were rarely seen. There were no significant differences between demographic data in asthmatic patients with positive compared to those with negative LUS. This positive LU scan rate is in keeping with a prior study on LU in pediatrics.

Evaluation of Supranormal Spirometry Values With an Obstructive Ratio for Airway Hyperreactivity.

Published guidelines on spirometry interpretation suggest an elevated FVC and FEV1 > 100% of predicted with an obstructive ratio may represent a physiological variant. Further evidence is needed on whether this finding indicates symptomatic airways obstruction and what additional evaluation should be done. Participants were prospectively enrolled to undergo additional testing for a technically adequate spirometry study with an FEV1 > 90% of predicted, and FEV1/FVC below the lower limit of normal, based on 95th percentile confidence intervals. Further testing consisted of full pulmonary function testing, impulse oscillometry (IOS), post-bronchodilator testing, fractional exhaled nitric oxide (FeNO), and methacholine challenge testing (MCT). A total of 49 patients meeting entry criteria enrolled and completed testing. Thirty-three were considered symptomatic based on clinical indications for initial testing and 16 were considered asymptomatic. Baseline pulmonary function test values were not different between groups while IOS R5 values (% predicted) were higher in the symptomatic group (126.5 ± 0.37 vs 107.1 ± 0.31). Bronchodilator responsiveness on PFT or IOS was infrequent in both groups. There was a 29% positivity rate for MCT in the symptomatic group compared to one borderline study in asymptomatic participants. FeNO was similar for symptomatic, 26.17 ± 31.3 ppb, compared to asymptomatic, 22.8 ± 13.5 ppb (p = 0.93). The dysanapsis ratio was higher in the symptomatic (0.15 ± 0.03) compared to the asymptomatic (0.13 ± 0.02) (p < 0.05). Normal FEV1 > 90% of predicted and obstructive indices may not represent a normal physiological variant in all patients. In symptomatic patients, a positive MCT and elevated baseline IOS values were more common than in asymptomatic patients with similar PFT characteristics. These findings suggest that clinicians should still evaluate for airway hyperresponsiveness in patients with exertional dyspnea with airway obstruction and FEV1 > 90% of predicted and consider alternative diagnoses to include a normal physiologic variant if non-reactive.

The value of small airway function parameters and fractional exhaled nitric oxide for predicting positive methacholine challenge test in asthmatics of different ages with FEV1 ≥80% predicted.

BackgroundSmall airway function parameters (SAFPs) combined with fractional exhaled nitric oxide (FeNO) can predict a positive methacholine challenge test (MCT) for asthma diagnosis. However, their predictive utility in patients with forced expiratory volume in one second (FEV1) ≥80% predicted within different age ranges remains unclear. This study aimed to assess the utility of SAFPs, alone or combined with FeNO, to predict a positive MCT in patients in two age groups (<55 and ≥55 years) with asthma‐suggestive symptoms and FEV1 ≥80% predicted.MethodsWe enrolled 846 Chinese patients with suspected asthma and standard spirometry, FeNO, and MCT findings. Using the area under the curves (AUCs), the utility of SAFPs, alone or combined with FeNO, for predicting a positive MCT was analyzed in a discovery (n = 534) and validation cohort (n = 312) in both age groups with FEV1 ≥80% predicted.ResultsIn the discovery cohort, the optimal cut‐off values for predicting a positive MCT in patients aged <55 years (74.2% and 74.9% for forced expiratory flow (FEF)50% and FEF25%–75%, respectively) were higher than those in patients aged ≥55 years (65.0% and 62.9% for FEF50%, FEF25%–75%, respectively). However, the optimal FeNO value in patients aged <55 years (43 ppb) was lower than that in patients aged ≥55 years (48 ppb). FeNO combined with SAFPs (FEF50%, FEF25%–75%) significantly increased the AUCs in both groups (≥55 years [0.851 for FEF50% and 0.844 for FEF25%–75%]; <55 years [0.865 for FEF50% and 0.883 for FEF25%–75%]) compared with a single parameter (p < 0.05). These findings were confirmed in the validation cohort. Compared with patients ≥55 years, those aged <55 years had higher and lower optimal cut‐off values for SAFPs and FeNO, respectively. The AUCs of FeNO combined with SAFPs for predicting a positive MCT for asthma diagnosis were significantly higher than those of the individual parameters (p < 0.05) in both age groups.ConclusionsThere were age‐group differences in the utility of SAFPs combined with FeNO for predicting a positive MCT. Patients with an asthma‐suggestive history and a normal FEV1 should be stratified by age when using SAFPs combined with FeNO to predict a positive MCT.

Airway hyperresponsiveness in patients with normal spirometry results and symptoms compatible with asthma: Primary care retrospective chart review.

To evaluate the proportion of patients with symptoms suggestive of asthma and normal lung function who exhibit airway hyperreactivity with methacholine challenge testing (MCT) in primary care. Retrospective chart review. Primary care lung clinic in Toronto, Ont. A total of 69 patients presenting to the lung clinic who had symptoms compatible with asthma, normal spirometry test results, and were referred for MCT. Descriptive statistics, frequency counts, independent t tests, and 2 tests were used to examine differences in the proportion of clinical and demographic variables identified in patients with or without a positive MCT result. Effect size was determined between MCT-positive and MCT-negative patients for both categorical ( coefficient) and continuous (Hedges g) data. Twenty-one patients (30.4%) had positive MCT results, and 48 patients (69.6%) had negative MCT results. Family history of asthma and reduced baseline and postbronchodilator forced expiratory volume in 1 second were associated with a positive MCT result. The findings of this study provide insight into the utility of simple spirometry for asthma diagnosis and the need to further clarify the role of MCT in the primary care setting.

Performance Characteristics of Spirometry With Negative Bronchodilator Response and Methacholine Challenge Testing and Implications for Asthma Diagnosis

In patients with a history suggestive of asthma, diagnosis is usually confirmed by spirometry with bronchodilator response (BDR) or confirmatory methacholine challenge testing (MCT). We examined the proportion of participants with negative BDR testing who had a positive MCT (and its predictors) result and characteristics of MCT, including effects of controller medication tapering and temporal variability (and predictors of MCT result change), and concordance between MCT and pulmonologist asthma diagnosis. Adults with self-reported physician-diagnosed asthma were recruited by random-digit dialing across Canada. Subjects performed spirometry with BDR testing and returned for MCT if testing was nondiagnostic for asthma. Subjects on controllers underwent medication tapering with serial MCTs over 3 to 6weeks. Subjects with a negative MCT (the provocative concentration of methacholine that results in a 20%drop in FEV1 [PC20] > 8mg/mL) off medications were examined by a pulmonologist and had serial MCTs after 6 and 12months. Of 500 subjects (50.5 ± 16.6 years old, 68.0%female) with a negative BDR test for asthma, 215 (43.0%) had a positive MCT. Subjects with prebronchodilator airflow limitation were more likely to have a positive MCT (OR, 1.90; 95%CI, 1.17-3.04). MCT converted from negative to positive, with medication tapering in 18 of 94 (19.1%) participants, and spontaneously over time in 25 of 165 (15.2%) participants. Of 231 subjects with negative MCT, 28 (12.1%) subsequently received an asthma diagnosis from a pulmonologist. In subjects with a self-reported physician diagnosis of asthma, absence of bronchodilator reversibility had a negative predictive value of only 57%to exclude asthma. A finding of spirometric airflow limitation significantly increased chances of asthma. MCT results varied with medication taper and over time, and pulmonologists were sometimes prepared to give a clinical diagnosis of asthma despite negative MCT. Correspondingly, in patients for whom a high clinical suspicion of asthma exists, repeat testing appears to be warranted.

Current Bronchodilator Responsiveness Criteria Underestimate Asthma in Older Adults.

Asthma is common in older adults and is confirmed by demonstration of variable expiratory air-flow limitations, typically evaluated by spirometric assessment of bronchodilator responsiveness. However, many patients with clinically suspected asthma and documented air-flow obstruction do not exhibit a post-bronchodilator response that meets or exceeds current established guidelines. We investigated if extending the time from bronchodilator administration to assessment of bronchodilator response increases the yield of spirometry for the diagnosis of asthma in older adults. This was a cross-sectional study. The subjects were non-smokers, ≥ 60y old, and with suspected asthma. Subjects were characterized as (1) those with a positive bronchodilator response on the 30-min post-bronchodilator spirometry, (2) those with a positive bronchodilator response on the 60-min post-bronchodilator spirometry, and (3) those without a positive bronchodilator response but with a positive methacholine challenge test. Factors associated with a late response to bronchodilator were evaluated by using bivariate analysis and by multivariate analysis by using a logistic regression model. This study enrolled 165 subjects. Of these, 81 (49.1%) had a positive bronchodilator response on 30-min post-bronchodilator spirometry; 25 (15.2%) had a positive bronchodilator response on the 1-h post-bronchodilator spirometry; and 59 (35.8%) had no positive bronchodilator response but had a positive methacholine challenge test. On multivariable regression analysis, those with a higher baseline percentage of predicted FEV1, higher scores on a standard asthma control test, and wheezing and/or cough after exercise were more likely to either have a late bronchodilator response or no bronchodilator response. Our study showed that a late positive response to bronchodilator use was more common than previously presumed in older subjects with suspected asthma. Pulmonary function testing laboratories should consider routinely reassessing spirometry at 1 h after bronchodilator use if the earlier assessment did not reveal a significant response.

Broncholithiasis Masquerading as Asthma

Broncholithiasis is the presence of osteoid material molded in the bronchial lumen.1Krishnan S. Kniese C.M. Mankins M. Heitkamp D.E. Sheski F.D. Kesler K.A. Management of broncholithiasis.J Thorac Dis. 2018; 10: S3419-S3427Crossref Scopus (10) Google Scholar It produces chronic inflammation leading to airway obstruction mimicking asthma. A 52-year-old lifelong nonsmoker woman complained of constant, progressive, dry cough for 3 months. The patient denied precipitating factors, previous events, and aggravating or alleviating factors. Her cough was associated with halitosis, subjective weight loss, chest tightness, wheezing, urinary stress incontinence, and dyspnea. Past medical history was significant for exercise-induced bronchospasm, she denied the use of prescribed or over-the-counter medication, and the physical examination revealed expiratory wheezing. On the basis of findings, we diagnosed asthma. The result of the methacholine challenge was positive; nonetheless, the patient did not improve after a trial of 2 dry-powder inhalers with high-dose inhaled corticosteroids/long-acting beta-agonist (fluticasone propionate/salmeterol and fluticasone furoate/vilanterol), and systemic steroids. Two episodes of pneumonia complicated her course, and a chest computed tomography performed after the second episode revealed a broncholith in the right bronchus (Figure 1). Finally, the foreign material was extracted with a bronchoscope (Figure 2), leading to complete symptomatic relief.Figure 2Broncholith material after bronchoscopic removal.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Most cases of broncholithiasis are secondary to chronic lymphadenitis caused by histoplasmosis, foreign body aspiration, ossified bronchial cartilage, and osteoid material migration from other parts of the body.1Krishnan S. Kniese C.M. Mankins M. Heitkamp D.E. Sheski F.D. Kesler K.A. Management of broncholithiasis.J Thorac Dis. 2018; 10: S3419-S3427Crossref Scopus (10) Google Scholar Patients often present with chronic cough, dysphagia, lithoptysis, hemoptysis, and recurrent pneumonias.1Krishnan S. Kniese C.M. Mankins M. Heitkamp D.E. Sheski F.D. Kesler K.A. Management of broncholithiasis.J Thorac Dis. 2018; 10: S3419-S3427Crossref Scopus (10) Google Scholar Often, findings in x-rays are nonspecific (hilar calcification or parenchymal infiltrates, depending on the etiology), so a computed tomography is required to diagnose, localize, and detect the degree of airway obstruction.1Krishnan S. Kniese C.M. Mankins M. Heitkamp D.E. Sheski F.D. Kesler K.A. Management of broncholithiasis.J Thorac Dis. 2018; 10: S3419-S3427Crossref Scopus (10) Google Scholar Clinical management is preferred over surgery because of the risk of bleeding; however, severe cases require bronchoscopic or surgical extraction.1Krishnan S. Kniese C.M. Mankins M. Heitkamp D.E. Sheski F.D. Kesler K.A. Management of broncholithiasis.J Thorac Dis. 2018; 10: S3419-S3427Crossref Scopus (10) Google Scholar In conclusion, broncholithiasis can produce airway obstruction and chronic inflammation resembling asthma.1Krishnan S. Kniese C.M. Mankins M. Heitkamp D.E. Sheski F.D. Kesler K.A. Management of broncholithiasis.J Thorac Dis. 2018; 10: S3419-S3427Crossref Scopus (10) Google Scholar Physicians must consider alternative diagnoses in patients with atypical asthma, unresponsive to medical treatment in spite of a positive methacholine challenge test result.2Coates A.L. Wanger J. Cockcroft D.W. Culver B.H. Carlsen K. Diamant Z. et al.ERS technical standard on bronchial challenge testing: general considerations and performance of methacholine challenge tests.Eur Respir J. 2017; 49: 1601526Crossref PubMed Scopus (176) Google Scholar

METABOLIC SYNDROME BIOMARKERS OF WORLD TRADE CENTER AIRWAY HYPERREACTIVITY: A 16-YEAR PROSPECTIVE COHORT STUDY

Airway hyperreactivity (AHR) related to environmental exposure is a significant public health risk worldwide. Similarly, metabolic syndrome (MetSyn), a risk factor for obstructive airway disease (OAD) and systemic inflammation, is a significant contributor to global adverse health. This prospective cohort study followed N = 7486 World Trade Center (WTC)-exposed male firefighters from 11 September 2001 (9/11) until 1 August 2017 and investigated N = 539 with newly developed AHR for clinical biomarkers of MetSyn and compared them to the non-AHR group. Male firefighters with normal lung function and no AHR pre-9/11 who had blood drawn from 9 September 2001-24 July 2002 were assessed. World Trade Center-Airway Hyperreactivity (WTC-AHR) was defined as either a positive bronchodilator response (BDR) or methacholine challenge test (MCT). The electronic medical record (EMR) was queried for their MetSyn characteristics (lipid profile, body mass index (BMI), glucose), and routine clinical biomarkers (such as complete blood counts). We modeled the association of MetSyn characteristics at the first post-9/11 exam with AHR. Those with AHR were significantly more likely to be older, have higher BMIs, have high intensity exposure, and have MetSyn. Smoking history was not associated with WTC-AHR. Those present on the morning of 9/11 had 224% increased risk of developing AHR, and those who arrived in the afternoon of 9/11 had a 75.9% increased risk. Having ≥3 MetSyn parameters increased the risk of WTC-AHR by 65.4%. Co-existing MetSyn and high WTC exposure are predictive of future AHR and suggest that systemic inflammation may be a contributor.

Metabolic Syndrome Biomarkers of World Trade Center Airway Hyperreactivity: A 16-Year Prospective Cohort Study.

Airway hyperreactivity (AHR) related to environmental exposure is a significant public health risk worldwide. Similarly, metabolic syndrome (MetSyn), a risk factor for obstructive airway disease (OAD) and systemic inflammation, is a significant contributor to global adverse health. This prospective cohort study followed N = 7486 World Trade Center (WTC)-exposed male firefighters from 11 September 2001 (9/11) until 1 August 2017 and investigated N = 539 with newly developed AHR for clinical biomarkers of MetSyn and compared them to the non-AHR group. Male firefighters with normal lung function and no AHR pre-9/11 who had blood drawn from 9 September 2001–24 July 2002 were assessed. World Trade Center-Airway Hyperreactivity (WTC-AHR) was defined as either a positive bronchodilator response (BDR) or methacholine challenge test (MCT). The electronic medical record (EMR) was queried for their MetSyn characteristics (lipid profile, body mass index (BMI), glucose), and routine clinical biomarkers (such as complete blood counts). We modeled the association of MetSyn characteristics at the first post-9/11 exam with AHR. Those with AHR were significantly more likely to be older, have higher BMIs, have high intensity exposure, and have MetSyn. Smoking history was not associated with WTC-AHR. Those present on the morning of 9/11 had 224% increased risk of developing AHR, and those who arrived in the afternoon of 9/11 had a 75.9% increased risk. Having ≥3 MetSyn parameters increased the risk of WTC-AHR by 65.4%. Co-existing MetSyn and high WTC exposure are predictive of future AHR and suggest that systemic inflammation may be a contributor.

ROCK, PAPER, SCISSORS, ASTHMA, BRONCH: ROCK BEATS ASTHMA

Introduction Broncholithiasis occurs due to calcified substance found in the bronchial tree. Patients present with wheezing, cough, shortness of breath, and less commonly lithoptysis. Broncholiths can result in recurrent post obstructive pneumonia and bronchiectasis. In symptomatic patients, rigid or flexible bronchoscopy is often needed. We present a case of broncholithiasis and treatment with bronchoscope removal. Case Description A 52-year-old female non-smoker was evaluated for a three-year history of non-productive cough, globus sensation, shortness of breath, wheezing, fatigue, halitosis, and weight loss. She had a history of two episodes of chest x-ray proven pneumonia. Physical examination revealed expiratory wheezing. A sinus CT scan was normal. Patient had a positive methacholine challenge test. However, the patient did not respond to high dose inhaled corticosteroid/long-acting beta-agonist inhalers or systemic steroids for asthma. As this was an atypical presentation for asthma and the patient did not respond to standard therapy, further testing was performed. After CT of the chest showed a broncholith in a right sided bronchus, flexible bronchoscopy was utilized to remove the broncholith (Fig. 1). She subsequently felt immediate relief and the symptoms subsided. After the procedure, patient recalled possible lithoptysis a few months earlier. Discussion This case demonstrates the importance of further investigation even with a positive methacholine challenge test in a patient with recurrent pneumonia where patient symptoms do not clearly fit the clinical picture of asthma. Recognition of this process is critical in symptomatic patients for bronchoscope therapy for symptom relief.

Evaluation of Soluble CD48 Levels in Patients with Allergic and Nonallergic Asthma in Relation to Markers of Type 2 and Non-Type 2 Immunity: An Observational Study.

CD48 is a costimulatory receptor associated with human asthma. We aimed to assess the significance of the soluble form of CD48 (sCD48) in allergic and nonallergic asthma. Volunteer patients completed an asthma and allergy questionnaire, spirometry, methacholine challenge test, a common allergen skin prick test, and a complete blood count. sCD48, IgE, IL5, IL17A, IL33, and IFNγ were quantitated in serum by ELISA. Asthma was defined as positive methacholine challenge test or a 15% increase in FEV1 post bronchodilator in symptomatic individuals. Allergy was defined as positive skin test or IgE levels > 200 IU/l in symptomatic individuals. 137 individuals participated in the study: 82 (60%) were diagnosed with asthma of which 53 (64%) was allergic asthma. sCD48 levels were significantly elevated in patients with nonallergic asthma compared to control and to the allergic asthma cohort (median (IQR) pg/ml, 1487 (1338–1758) vs. 1308 (1070–1581), p < 0.01, and 1336 (1129–1591), p = 0.02, respectively). IL17A, IL33, and IFNγ levels were significantly elevated in allergic and nonallergic asthmatics when compared to control. No correlation was found between sCD48 level and other disease markers. sCD48 is elevated in nonallergic asthma. Additional studies are required for understanding the role of sCD48 in airway disease.