Methacholine Challenge Research Articles

Metformin Alleviates Airway Hyperresponsiveness in a Mouse Model of Diet-Induced Obesity.

Obese asthma is a unique phenotype of asthma characterized by non-allergic airway hyperresponsiveness (AHR) and inflammation which responds poorly to standard asthma therapy. Metformin is an oral hypoglycemic drug with insulin-sensitizing and anti-inflammatory properties. The objective of the current study was to test the effect of metformin on AHR in a mouse model of diet-induced obesity (DIO). We fed 12-week-old C57BL/6J DIO mice with a high fat diet for 8 weeks and treated them with either placebo (control, n = 10) or metformin (n = 10) added in drinking water (300 mg/kg/day) during the last 2 weeks of the experiment. We assessed AHR, metabolic profiles, and inflammatory markers after treatments. Metformin did not affect body weight or fasting blood glucose, but significantly reduced serum insulin (p = 0.0117). Metformin reduced AHR at 30 mg/ml of methacholine challenge (p = 0.0052) without affecting baseline airway resistance. Metformin did not affect circulating white blood cell counts or lung cytokine mRNA expression, but modestly decreased circulating platelet count. We conclude that metformin alleviated AHR in DIO mice. This finding suggests metformin has the potential to become an adjuvant pharmacological therapy in obese asthma.

Pulmonary Procedures During the COVID-19 Pandemic: A Work Group Report of the AAAAI Asthma Diagnosis and Treatment (ADT) Interest Section

The COVID-19 pandemic has placed increased demands on the ability to safely perform pulmonary procedures in keeping with Centers for Disease Control and Prevention (CDC), American Thoracic Society (ATS), and the Occupational Safety and Health Administration (OSHA) recommendations. Accordingly, the American Academy of Allergy, Asthma & Immunology (AAAAI) Asthma Diagnosis and Treatment convened this work group to offer guidance. The work group is composed of specialist practitioners from academic and both large and small practices. Individuals with special expertise were assigned sections on spirometry, fractional exhaled nitric oxide, nebulized treatments, and methacholine challenge. The work group met periodically to achieve consensus. This resulting document has recommendations for the allergy/asthma/immunology health care setting based on available evidence including reference documents from the CDC, ATS, and OSHA.

Characterizing pediatric lung ultrasound findings during a chemically induced bronchospasm.

Lung ultrasound (LUS) has been shown to be a useful clinical tool in pediatrics, but very little is known about the LUS findings of asthma in children. The primary objective was to characterize LUS findings of pediatric patients before and after a chemically induced bronchospasm. The secondary objective was to evaluate the effect of bronchodilators on LUS findings. Eligible children 6-17 years old presenting for a methacholine challenge test (MCT) in a pediatric respiratory clinic were recruited. Patients with viral symptoms were excluded. A six-zone LUS protocol was performed before and after the MCT, and after bronchodilator administration; video recordings were analysed by an expert blinded to the patient characteristics and MCT results. Forty-four patients were included in the study. Fivepatients had positive LUS findings at baseline. Ninepatients out of 29 (31%) had new-onset positive LUS following a reactive MCT. There was a significant association between having a chemically induced bronchospasm and a positive LUS post-MCT (odds ratio [95%confidence interval]: 5.3 [1.0-27.7]; p = 0.05). Among patients who developed positive LUS findings post-MCT,fourout of ninereturned to having a negative LUS postbronchodilator administration. This is the first known report of an association between LUS findings and bronchospasm in pediatric patients. It is also the first documentation of resolution of LUS findings postbronchodilator administration. Most LUS findings observed were small and limited to a few intercostal spaces. Further research is required to quantify these findings and evaluate the effect of salbutamol on LUS.

Bronchodilatory effect of higenamine as antiallergic asthma treatment

Asthma is a complex airway disease that affects more than 350 million humans worldwide. Allergic asthma symptoms are induced by Th2 immune response with the release of cytokines and allegro-inflammatory...

Wheeze is an unreliable endpoint for bronchial methacholine challenges in preschool children.

BackgroundOnset of wheeze is the endpoint often used in the determination of a positive bronchial challenge test (BCT) in young children who cannot perform spirometry. We sought to assess several clinical endpoints at the time of a positive BCT in young children with recurrent wheeze compared to findings in school‐aged children with asthma.MethodsPositive BCT was defined in: (1) preschool children (n = 22) as either persistent cough, wheeze, fall in oxygen saturation (SpO2) of ≥5%, or ≥50% increase in respiratory rate (RR) from baseline; and (2) school‐aged children (n = 22) as the concentration of methacholine (MCh) required to elicit a 20% decline in FEV1 (PC20).ResultsAll preschool children (mean age 3.4 years) had a positive BCT (median provocative MCh concentration 1.25 mg/ml [IQR, 0.62, 1.25]). Twenty (91%) school‐aged children (mean age 11.3 years) had a positive BCT (median PC20 1.25 mg/ml [IQR, 0.55, 2.5]). At the time of the positive BCT, the mean fall in SpO2 (6.9% vs. 3.8%; p = .001) and the mean % increase in RR (61% vs. 22%; p < .001) were greater among preschool‐aged than among school‐aged children. A minority of children developed wheeze at time of positive BCT (23% preschool‐ vs. 15% school‐aged children; p = .5).ConclusionsThe use of wheeze as an endpoint for BCT in preschool children is unreliable, as it rarely occurs. The use of clinical endpoints, such as ≥25% increase in RR or fall in SpO2 of ≥3%, captured all of our positive BCT in preschool children, while minimizing undue respiratory distress.

Work-related allergy and asthma associated with cleaning agents in health workers in Southern African tertiary hospitals.

Health workers (HWs) are exposed to diverse cleaning agents in large hospitals. This study determined the prevalence of work-related symptoms, allergic sensitization, and lung function abnormalities in HWs of two tertiary hospitals in Southern Africa. A cross-sectional study of 699 HWs (South Africa: SAH, n = 346; Tanzania: TAH, n = 353) was conducted. Health outcomes were assessed using a standardized ECRHS questionnaire, immunological tests (specific IgE antibody to common aero-allergens and to occupational allergens: natural rubber latex [NRL] Hev b5 and Hev b6.02, chlorhexidine, and ortho-phthalaldehyde [OPA]), spirometry [pre-and post- bronchodilator], methacholine challenge, and fractional exhaled nitric oxide (FeNO). A large proportion of participants (78%) were women. Median age was 42 years, with 76% nurses, 12% cleaners, and 5% administrative workers. Current smoking was more common in SAHWs (12%) than TAHWs (1%). The overall prevalence of doctor-diagnosed asthma was 7%. Atopy was present in 43% of HWs, while 4% were sensitized to OPA, 2% to NRL, and 1% to chlorhexidine. Prevalence of work-related ocular-nasal symptoms (16%) was higher than skin (12%) and chest (7%) symptoms. TAHWs had significantly lower mean lung volumes, higher degrees of significant airflow obstruction and impaired lung function. The prevalence of bronchial hyperresponsiveness in SAHWs (14%) was high. Overall, 23% of HWs had abnormal FeNO; 6% having high (>50 ppb) levels. FeNO was positively associated with sensitization to occupational allergens, primarily OPA and NRL. HWs from both hospitals had similar prevalence of work-related respiratory symptoms. Sensitization to OPA and NRL appears to be contributing to allergic airway inflammation in these HWs.

The role of small airway dysfunction in asthma control and exacerbations: a longitudinal, observational analysis using data from the ATLANTIS study

Although small airway disease is a feature of asthma, its association with relevant asthma outcomes remains unclear. The ATLANTIS study was designed to identify the combination of physiological and imaging variables that best measure the presence and extent of small airway disease in asthma, both cross-sectionally and longitudinally. In this longitudinal analysis, we evaluated which small airway parameters studied were most strongly associated with asthma control, exacerbations, and quality of life. In this observational cohort study, participants with mild, moderate, or severe stable asthma were recruited between June 30, 2014, and March 3, 2017, via medical databases and advertisements in nine countries worldwide. Eligible participants were aged 18-65 years with a clinical asthma diagnosis for at least 6 months. Participants were followed up for 1 year, with visits at baseline, 6 months, and 12 months. Physiological tests included spirometry, lung volumes, impulse oscillometry, multiple breath nitrogen washout (MBNW), and percentage decrease in forced vital capacity during methacholine challenge. CT densitometry was performed to evaluate small airway disease. We examined the associations between these measurements and asthma exacerbations, asthma control, and quality of life using univariate and multivariate analyses. A composite ordinal score comprising percent predicted R5-20 (resistance of small-to-mid-sized airways), AX (area of reactance), and X5 (reactance of more central, conducting small airways at 5 Hz) was constructed. 773 participants (median age 46 years [IQR 34-54]; 450 [58%] female) were included in this longitudinal study. Univariate analyses showed that components of impulse oscillometry, lung volumes, MBNW, and forced expiratory flow at 25-75% of FVC were significantly correlated with asthma control and exacerbations (Spearman correlations 0·20-0·25, p<0·0001 after Bonferroni correction). As a composite of impulse oscillometry, the ordinal score independently predicted asthma control and exacerbations in a multivariate analysis with known exacerbation predictors. CT parameters were not significantly correlated with asthma control, exacerbation, or quality of life. Small airway disease, as measured by physiological tests, is longitudinally associated with clinically important asthma outcomes, such as asthma control and exacerbations. Chiesi Farmaceutici.

A Breathtaking Hernia: A Giant Hiatal Hernia Masquerading as Poorly Controlled Asthma

A 93-year-old female presented with persistent shortness of breath and wheezing since the consumption of a meal. Her past medical history is significant for a clinical diagnosis of asthma at the age of 88 years, without pulmonary function testing, complicated by several prior visits to the emergency department (ED) for recurrent exacerbations. Multiple bronchodilators in the ED provided only minimal improvement in her symptoms. Chest imaging eventually revealed a giant, fluid-filled hiatal hernia exhibiting a compressive effect on the posterior aspect of the left atrium. The etiology of the patient's airway bronchoconstriction was likely multifactorial. We hypothesize that the extrinsic, dynamic compression of the bronchial tree by the peristaltic motion of the hiatal hernia, microaspiration from gastroesophageal reflux, and peribronchial edema from left atrial compression accounted for our patient's unique presentation. An outpatient methacholine challenge test eventually excluded bronchial asthma. Although she was considered a poor surgical candidate, she has had no further recurrences of her symptoms with counseling on conservative lifestyle changes. This case serves to highlight the heterogeneity in presentations of hiatal hernias, particularly in elderly females. Furthermore, it remains prudent to maintain a broad differential for wheezing, as evidenced by our patient who was previously managed for a number of years as poorly controlled asthma.

Clinical significance and applications of oscillometry.

Recently, "Technical standards for respiratory oscillometry" was published, which reviewed the physiological basis of oscillometric measures and detailed the technical factors related to equipment and test performance, quality assurance and reporting of results. Here we present a review of the clinical significance and applications of oscillometry. We briefly review the physiological principles of oscillometry and the basics of oscillometry interpretation, and then describe what is currently known about oscillometry in its role as a sensitive measure of airway resistance, bronchodilator responsiveness and bronchial challenge testing, and response to medical therapy, particularly in asthma and COPD. The technique may have unique advantages in situations where spirometry and other lung function tests are not suitable, such as in infants, neuromuscular disease, sleep apnoea and critical care. Other potential applications include detection of bronchiolitis obliterans, vocal cord dysfunction and the effects of environmental exposures. However, despite great promise as a useful clinical tool, we identify a number of areas in which more evidence of clinical utility is needed before oscillometry becomes routinely used for diagnosing or monitoring respiratory disease.

Pulmonary function testing for the diagnosis of asthma in preschool children.

To highlight the recent evidence of the lung function techniques used in preschool children to diagnose asthma. Several techniques are available to measure lung function and airway inflammation in preschool children, including spirometry (from age 5 years), impulse oscillometry (>3 years), whole-body plethysmography (>3 years), fractional exhaled nitric oxide (FeNO) (>5 years), multiple breath washout (>3 years), structured light plethysmography (>1-2 years) and impedance pneumography (>1 years). If applicable, measuring forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC) ratio using spirometry is useful (cut-off < 80% predicted or below lower limit of normal [LLN] defined as z-score < -1.64) for diagnosing preschool asthma. For those unable to perform spirometry, whole-body plethysmography (sRaw > 1.6 kPa/s) and impulse oscillometry (Rrs and Xrs at 5 Hz z-score > 2) may be useful. Adding a bronchodilator reversibility test (FEV1 increase > 12%, sRaw decrease > 25-30%, Rrs at 5 Hz decrease > 40%) or a bronchial challenge test, for example, exercise test (FEV1 decrease > 10%), may improve the sensitivity of these tests. Elevated FeNO (>25-35 ppb) is a promising adjunctive test for diagnosing preschool asthma. With trained personnel, lung function testing can be done with high reliability even in children between 2 and 4 years of age. To avoid over and undertreatment of asthma, objective measurement of lung function is clinically important in preschool children.

Effects of Local Nasal Immunotherapy with FIP-fve Peptide and Denatured Tyrophagus putrescentiae for Storage Mite-Induced Airway Inflammation.

Allergic diseases are affecting public health and have increased over the last decade. Sensitization to mite allergens is a considerable trigger for allergy development. Storage mite-Tyrophagus putrescentiae shows great significance of allergenic potential and clinical relevance. The fungal immunomodulatory peptide FIP-fve has been reported to possess immunomodulatory activity. We aimed to determine whether T. putrescentiae-induced sensitization and airway inflammation in mice could be downregulated by FIP-fve in conjunction with denatured T. putrescentiae (FIP-fve and DN-Tp). Immune responses and physiologic variations in immunoglobulins, leukocyte subpopulations, cytokine productions, pulmonary function, lung pathology, cytokines in CD4+ and Treg cells were evaluated after local nasal immunotherapy (LNIT). After the LNIT with FIP-fve and DN-Tp, levels of specific IgE, IgG1, and IgG2a in the sera and IgA in the bronchoalveolar lavage fluid (BALF) were significantly reduced. Infiltrations of inflammatory leukocytes (eosinophils, neutrophils, and lymphocytes) in the airway decreased significantly. Production of proinflammatory cytokines (IL-5, IL-13, IL-17F and IL-23) and chemokine (IL-8) were significantly reduced, and Th1-cytokine (IL-12) increased in the airway BALF after LNIT. Pulmonary functions of Penh values were significantly decreased after the methacholine challenge, which resulted in a reduction of airway hypersensitivity after LNIT. Bronchus pathology showed a reduction of inflammatory cell infiltration and epithelium damage after LNIT. The IL-4+/CD4+ T cells could be downregulated and the IFN-γ+/CD4+ T cells upregulated. The Treg-related immunity of IL-10 and Foxp3 expressions in CD4+CD25+ cells were both upregulated after LNIT. In conclusion, LNIT with FIP-fve and DN-Tp had an anti-inflammatory effect on mite-induced airway inflammations and possesses potential as an immunomodulatory therapy agent for allergic airway diseases.

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.

Bronchial Hyper-responsiveness in Post-tubercular Patients: A Case-control Study

Introduction: Bronchial hyper-responsiveness is the manifestation of excessive bronchoconstriction in response to diverse types of stimuli both physical and chemical. It is the most characteristic feature of bronchial asthma; it also occurs in a spectrum of other diseases like Chronic Obstructive Pulmonary Disorders (COPD) and reactive airway syndrome and may be provoked by a variety of stimuli like histamine and methacholine. Patients of healed pulmonary Tuberculosis (TB) show varying extent of lung impairment such as fibrosis, collapse, emphysema and broncho alveolar destruction. Aim: To assess the incidence and severity of obstructive airway diseases in previously treated TB patients. Materials and Methods: This was a prospective case control study, carried out in the Department of Tuberculosis and Respiratory Diseases, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh, India, from September 2017 to September 2019, this study included 120 patients of previously treated TB, who were divided into two groups. The case group (71) included patients who completed treatment for TB and had dyspnoea. The control group (49) consisted of patients who completed the treatment but did not have dyspnoea. The patients were subjected to spirometry, histamine bronchial challenge test and computed chest tomogram along with routine investigations including sputum for Acid Fast Bacilli (AFB). Results: The present study showed significant histamine hypersensitivity among post TB patients. In the case group, 34 (56%) patients showed positive response to bronchial challenge test with histamine; while in control group only 7 (14%) showed a positive response (p-value=0.004). Pulmonary function test (spirometry) showed an obstructive pattern in 35 (49%) case group patients, while normal pattern was the most common finding seen in 23 (47%) in the control group followed by obstruction in 10 (21%) patients. Among the cases, the mean Forced Expiratory Volume in the first second (FEV1) was 65.77±15.98, while among the controls, it was 80.02±8.81. The case group had a mean Forced Expiratory Volume in the first second/Forced Vital Capacity (FEV1/FVC) of 78.09±15.75, as against 81.33±16.79 in the control group. Conclusion: Airway bronchial hyper-reactivity is a prominent feature in previously treated tubercular patients. This underlines the need for proper attention towards post-tubercular lung function impairment and proper treatment of such patients so as to lessen the impact of bronchial hyper-reactivity on patient symptoms and their quality of life.

Análise da relação entre broncoespasmo induzido por exercício, aptidão cardiorrespiratória e nível de atividade física de adolescentes

ABSTRACT This study aims to verify the association between exercise-induced bronchospasm (EIB), cardiorespiratory fitness, and physical activity levels in adolescents. To do so, we evaluated 202 healthy adolescents aged from 13 to 18 years, out of which 94 (46.5%) were females and 108 (53.5%) males. Participants performed a bronchial challenge test in a treadmill (Master Super ATL, Inbramed®) to evaluate bronchial hyper-responsiveness; a spirometric test (Microquark, Cosmed®) to evaluate lung function; answered the Baecke’s Questionnaire of Habitual Physical Activity; and performed the progressive aerobic cardiovascular endurance run test. Data were analyzed using Spearman’s correlation, chi-square test, and odds ratio. The significance level adopted was p&lt;0.05. No statistically significant correlations were found between the decrease of the forced expiratory volume in the first second (FEV1), cardiorespiratory fitness, and physical activity levels. Likewise, the chi-squared test revealed no significant differences between classifications of cardiorespiratory fitness (low or adequate) and EIB (presence or absence) (χ2=0.155; p=0.694). Finally, odds ratio showed no increased chances of the presence of EIB in participants who presented low cardiorespiratory fitness (OR=1.130; CI: 0.616-2.073). We concluded that cardiorespiratory fitness and physical activity levels are not associated with the decrease of FEV1 and that there is no relation between the presence of EIB and the classification of cardiorespiratory fitness of adolescents.

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.

Effects of airway smooth muscle contraction and inflammation on lung tissue compliance.

There are renewed interests in using the parameter K of Salazar-Knowles' equation to assess lung tissue compliance. K either decreases or increases when the lung's parenchyma stiffens or loosens, respectively. However, whether K is affected by other common features of respiratory diseases, such as inflammation and airway smooth muscle (ASM) contraction, is unknown. Herein, male C57BL/6 mice were treated intranasally with either saline or lipopolysaccharide (LPS) at 1 mg/kg to induce pulmonary inflammation. They were then subjected to either a multiple or a single-dose challenge with methacholine to activate ASM to different degrees. A quasi-static pressure-driven partial pressure-volume (P-V) maneuver was performed before and after methacholine. The Salazar-Knowles' equation was then fitted to the deflation limb of the P-V loop to obtain K, as well as the parameter A, an estimate of lung volume (inspiratory capacity). The fitted curve was also used to derive the quasi-static elastance (Est) at 5 cmH2O. The results demonstrate that LPS and both methacholine challenges increased Est. LPS also decreased A, but did not affect K. In contradistinction, methacholine decreased both A and K in the multiple-dose challenge, whereas it decreased K but not A in the single-dose challenge. These results suggest that LPS increases Est by reducing the open lung volume (A) and without affecting tissue compliance (K), whereas methacholine increases Est by decreasing tissue compliance with or without affecting lung volume. We conclude that lung tissue compliance, assessed using the parameter K of Salazar-Knowles' equation, is insensitive to inflammation but sensitive to ASM contraction.

Predictors of Airway Hyperresponsiveness in Symptomatic Children with Normal Spirometry and Suspicious of Possible Asthma

Background: Asthma diagnosis may be challenging particularly in patients with mild symptoms without an obstructive pattern in spirometry. Detection of airway hyperresponsiveness (AHR) by a positive methacholine challenge (MCC) is still an important diagnostic tool to confirm the presence of asthma with reasonable certainty. However, it is time consuming and could be exhausting for patients. We aimed to identify the predictive factors for AHR in children with respiratory symptoms without obstructive pattern in spirometry. Methods: Data from children who had undergone MCC were analyzed retrospectively. The demographic features of patients along with laboratory results were collected. Results: A total of 123 children with a median age of 10.5 years were enrolled. AHR was detected in 81 children (65.8%). The age of the children with AHR was significantly younger. The prevalences of aeroallergen sensitization, nocturnal cough, wheezing, and a baseline forced expiratory flow at 75% of vital capacity (FEF75) <65% were significantly more frequent in children with AHR. Multivariate logistic regression analysis revealed age, ever wheezing, nocturnal cough, tree pollen allergy, and FEF75 <65% as independent predictors of AHR. A weighted clinical risk score was developed (range, 0–75 points). At a cutoff point of 35, the presence of AHR is predicted with a specificity of 90.5% and a positive predictive value of 91.5%. Conclusion: In children suspected of having asthma, but without an obstructive pattern in the spirometry, combining independent predictors, which can be easily obtained in clinical practice, might be used to identify children with AHR.

Additive effects of orchiectomy and intermittent hypoxia on lung mechanics and inflammation in C57BL/6J male mice.

What is the central question of this study? Does endogenous testosterone modulate the consequences of intermittent hypoxia (IH) in the lungs of male mice? What is the main finding and its importance? Orchiectomized mice exposed to IH develop a pattern that is similar to emphysema or obstructive lung disease with elevated lung volumes, low pulmonary elastance during a methacholine challenge test and high counts of lymphocytes in bronchoalveolar lavages. Since low testosterone levels and other respiratory diseases are common in sleep apnoea, there is a clear clinical relevance to these results. We tested the hypothesis that low testosterone levels modulate the pulmonary responses to intermittent hypoxia (IH; used as a model of sleep apnoea (SA)) in male mice. We used intact (SHAM) or orchiectomized (ORX) mice exposed to IH for 14days (12h/day, 10cycles/h, 6% oxygen) or to normoxia (Nx). We first measured ventilation and metabolic rates in freely behaving mice (whole-body plethysmography) and then respiratory mechanics in tracheotomized mice (flexiVent). We assessed the respiratory system resistance and elastance (Ers ), Newtonian resistance (resistance of the large airways), tissue damping and tissue elastance (H) under baseline conditions and during a methacholine challenge test. We also measured the quasi-static compliance and inspiratory capacity with partial pressure-volume loops. Finally, inflammatory cells were counted in the broncho-alveolar lavage (BAL) and we measured lung volume by water displacement. ORX-IH mice had higher tidal volume, inspiratory capacity and lung volume compared to the other groups, but showed signs of low efficiency of O2 exchange rate relative to minute ventilation. During the methacholine challenge, orchiectomy decreased the values of most mechanical parameters and IH reduced Ers and H leading to very low values in ORX-IH mice. Finally, the total number of cells and the number of lymphocytes in BAL were both increased by IH in ORX mice. Since reduced lung elasticity, low O2 extraction, increased lung volumes and inflammation are signs of emphysematous lung disease, we conclude that testosterone might prevent lung emphysema during IH exposures.

Aerosol Generation and Mitigation During Methacholine Bronchoprovocation Testing: Infection Control Implications in the Era of COVID-19.

Methacholine bronchoprovocation or challenge testing (MCT) is commonly performed to assess airway hyper-responsiveness in the setting of suspected asthma. Nebulization is an aerosol-generating procedure, but little is known about the risks of MCT in the context of the ongoing coronavirus disease 2019 (COVID-19) pandemic. We aimed to quantify and characterize aerosol generation during MCT by using different delivery methods and to assess the impact of adding a viral filter. Seven healthy subjects performed simulated MCT in a near particle-free laboratory space with 4 different nebulizers and with a dosimeter. Two devices continuously sampled the ambient air during the procedure, which detected ultrafine particles, from 0.02-1 μm, and particles of sizes 0.3, 0.5, 1.0, 2.0, 5.0, and 10 µm, respectively. Particle generation was compared among all the devices, with and without viral filter placement. Ultrafine-particle generation during simulated MCT was significant across all the devices. Ultrafine-particle (0.02-1 μm) concentrations decreased 77%-91% with the addition of a viral filter and varied significantly between unfiltered (P < .001) and filtered devices (P < .001). Ultrafine-particle generation was lowest when using the dosimeter with filtered Hudson nebulizer (1,258 ± 1,644 particle/mL). Ultrafine-particle concentrations with the filtered nebulizer devices using a compressor were higher than particle concentrations detected when using the dosimeter: Monaghan (3,472 ± 1,794 particles/mL), PARI (4,403 ± 2,948), Hudson (6,320 ± 1,787) and AirLife (9,523 ± 5,098). The high particle concentrations generated during MCT pose significant infection control concerns during the COVID-19 pandemic. Particle generation during MCT was significantly reduced by using breath-actuated delivery and a viral filter, which offers an effective mitigation strategy.

Prescribing inhalers: Choosing Wisely Canada interview with Dr Kimberly Wintemute.

![Figure][1]</img> Do not initiate medications for asthma (eg, inhalers, leukotriene receptor antagonists, or others) in patients 6 years of age and older who have not had confrmation of reversible airfow limitation with spirometry, and in its absence, a positive methacholine or exercise challenge