Respiratory Oscillometry and Functional Performance in Different COPD Phenotypes.

Purpose: Chronic obstructive pulmonary disease (COPD) phenotypes may introduce different characteristics that need to be known to improve treatment. Respiratory oscillometry provides a detailed analysis and may offer insight into the pathophysiology of COPD. In this paper, we used this method to evaluate the differences in respiratory mechanics of COPD phenotypes. Patients and Methods: This study investigated a sample of 83 volunteers, being divided into control group (CG = 20), emphysema (n = 23), CB (n = 20) and asthma-COPD overlap syndrome (ACOS, n = 20). These analyses were performed before and after bronchodilator (BD) use. Functional capacity was evaluated using the Glittre­ADL test, handgrip strength and respiratory pressures. Results: Initially it was observed that oscillometry provided a detailed description of the COPD phenotypes, which was consistent with the involved pathophysiology. A correlation between oscillometry and functional capacity was observed (r=-0.541; p = 0.0001), particularly in the emphysema phenotype (r = -0.496, p = 0.031). BD response was different among the studied phenotypes. This resulted in an accurate discrimination of ACOS from CB [area under the receiver operating curve (AUC) = 0.84] and emphysema (AUC = 0.82). Conclusion: These results offer evidence that oscillatory indices may enhance the comprehension and identification of COPD phenotypes, thereby potentially improving the support provided to these patients.

Bronchodilator response to albuterol nebulized with hypertonic saline in asthmatic children.

INTRODUCTION: Asthma is distinguished by bronchial obstruction reversible by bronchodilators. The first-line treatment for asthmatic exacerbations is the use of inhaled beta-agonists, by pressurized metered-dose inhalers or nebulized with normal saline solution (NSS). There are no reports of nebulized beta agonists' efficacy in asthmatic children when administered with hypertonic saline solution (HSS). OBJECTIVE: To evaluate bronchodilator responses (BDR) to albuterol nebulized with 3%-HSS in asthmatic children, compared to albuterol nebulized with NSS. POPULATION AND METHODS: In a prospective, experimental, double-blind, randomized clinical study, children with a confirmed diagnosis of asthma with mild or moderate bronchial obstruction (FEV1 40%-79% of predicted) were randomized to receive a nebulization with 2.5 mg of albuterol diluted in 3 cc of 3%-HSS or NSS (0.9%), by means of a jet nebulizer. After 30 min, the BDR was assessed. RESULTS: Fifty patients (mean age 12.0 ± 3 years, 29 males) were enrolled; 25 were randomized to the 3%-HSS group (FEV1 65.2% ± 10) and 25 to the NSS group (FEV1 69.1% ± 7.1). The BDR of FEV1 was 41.2% (SD: ±20.1; 95% confidence interval [CI]: 35.1-50.4) and 17.3% (SD: ±19.4; 95% CI: 9.7-24.9) (p < .0001) and of maximum mid-expiratory flow was 130% (SD: ±90.8; 95% CI: 94.6-166) and 69.8% (SD: ±72.5; 95% CI: 41.4-98.2) (p < .01), for the 3%-HSS and NSS groups, respectively. CONCLUSION: Albuterol produces a greater BDR when nebulized with 3%-HSS compared to NSS in asthmatic children with mild or moderate bronchial obstruction.

A comparative analysis of the bronchodilatador response measured by impulse oscillometry and spirometry in asthmatic children living at high altitude.

OBJECTIVE: Although the assessment of a bronchodilator response (BDR) is a routine and important procedure when performing lung function tests, comparisons between spirometric and oscillometric BDRs in asthmatic children living at high altitude have not been previously reported. The aim of the present study was to compare spirometric and oscillometric BDRs in children living at high altitude, and to identify independent predictors of spirometric and oscillometric BDRs. METHODS: Between January and December, 2015, asthmatic children aged between 5 and 17 years old performed impulse oscillometry (IOS) and spirometry during the same visit before and after albuterol administration. The data were analyzed, and children were classified into those positive for oscillometric BDR only, those positive for spirometric BDR only, those positive for both BDRs, and those negative for both BDRs. RESULTS: Ninety-three asthmatic children (56 boys, 37 girls), with a median (IQR) age of 11 (8-13) years, made up the study population. Among the total of 93 participants, 13 (14.0%), 4 (4.3%), 0 (0%), and 76 (81.7%) were positive for spirometric BDR only, positive for oscillometric BDR only, positive for both BDRs, and negative for both BDRs, respectively. Age and baseline lung function were identified as significant predictors of positive spirometric BDR. CONCLUSIONS: The present study shows poor concordance between positive spirometric and oscillometric BDRs, with a greater proportion of patients with a spirometric BDR when compared to those with positive oscillometric BDR. Additionally, age and baseline lung function are useful for predicting spirometric BDR results.

Depression, Asthma, and Bronchodilator Response in a Nationwide Study of US Adults.

BACKGROUND: Little is known about the relation between 2 common comorbidities (depression and anxiety) and asthma or bronchodilator response (BDR). OBJECTIVE: To examine the association between depressive symptoms and asthma or BDR in US adults. METHODS: Cross-sectional study of 20,272 adults aged 20 to 79 years from the 2007-2012 National Health and Nutrition Examination Survey. Depressive symptoms were measured using the 9-item Patient Health Questionnaire, and classified as none to minimal, mild, moderate, moderately severe, and severe. Major depression (comprising moderately severe to severe symptoms) was defined as a 9-item Patient Health Questionnaire score of 15 or more. Anxiety was defined as 5 or more days feeling anxious in the previous month. Current asthma was defined as having been diagnosed with asthma by a doctor or health professional and 1 or more asthma attack in the previous year. BDR (as percentage of baseline FEV1) was measured in 1356 participants with FEV1/forced vital capacity of less than 0.70 and/or FEV1 less than 70% of predicted. Logistic or linear regression was used for the multivariable analysis. RESULTS: Depressive symptoms were significantly and linearly associated with asthma, independently of anxiety symptoms. Subjects with major depression had 3.4 times higher odds of asthma than did those with minimal or no depressive symptoms (95% CI, 2.6-4.5; P < .01). Among adults with asthma, major depression was associated with a 4.2% reduction in BDR (95% CI, -7.5% to -0.8%; P = .02). Major depression was not associated with BDR among adults without asthma. Anxiety was not associated with asthma or BDR. CONCLUSIONS: Depressive symptoms are associated with asthma in adults, independently of anxiety symptoms. Major depression is associated with reduced BDR in adults with asthma.

Stress and Bronchodilator Response in Children with Asthma.

RATIONALE: Stress is associated with asthma morbidity in Puerto Ricans (PRs), who have reduced bronchodilator response (BDR). OBJECTIVES: To examine whether stress and/or a gene regulating anxiety (ADCYAP1R1) is associated with BDR in PR and non-PR children with asthma. METHODS: This was a cross-sectional study of stress and BDR (percent change in FEV1 after BD) in 234 PRs ages 9-14 years with asthma. We assessed child stress using the Checklist of Children's Distress Symptoms, and maternal stress using the Perceived Stress Scale. Replication analyses were conducted in two cohorts. Polymorphisms in ADCYAP1R1 were genotyped in our study and six replication studies. Multivariable models of stress and BDR were adjusted for age, sex, income, environmental tobacco smoke, and use of inhaled corticosteroids. MEASUREMENTS AND MAIN RESULTS: High child stress was associated with reduced BDR in three cohorts. PR children who were highly stressed (upper quartile, Checklist of Children's Distress Symptoms) and whose mothers had high stress (upper quartile, Perceived Stress Scale) had a BDR that was 10.2% (95% confidence interval, 6.1-14.2%) lower than children who had neither high stress nor a highly stressed mother. A polymorphism in ADCYAP1R1 (rs34548976) was associated with reduced BDR. This single-nucleotide polymorphism is associated with reduced expression of the gene for the ß2-adrenergic receptor (ADRB2) in CD4(+) lymphocytes of subjects with asthma, and it affects brain connectivity of the amygdala and the insula (a biomarker of anxiety). CONCLUSIONS: High child stress and an ADCYAP1R1 single-nucleotide polymorphism are associated with reduced BDR in children with asthma. This is likely caused by down-regulation of ADRB2 in highly stressed children.

Respuesta broncodilatadora en niños asmáticos / Bronchodilatador response in asthmatic children

In asthmatic patients the bronchodilator response (BDR) reflects airway obstruction reversibility. BDR commonly used definition of 12 percent or greater change in FEV1 from baseline offers poor sensitivity as an adjunct test in the diagnosis of asthma in children. A cutoff of 8 percent - 10 percent has significantly better sensitivity, although more research studies are needed to recommend this lower BDR value in children. A positive BDR is associated with biomarkers of inflammation, future lung function, inhaled corticosteroids response, and poor asthma control and could provide a useful tool for better monitoring asthmatic children, particularly when pre bronchodilator spirometry is in normal range.

En pacientes asmáticos la respuesta broncodilatadora (RBD) refleja la reversibilidad de la obstrucción de la vía aérea. La definición de 12 por ciento o mayor cambio en VEF1 con respecto a su basal tiene baja sensibilidad y podría llevar a un subdiagnóstico y subtratamiento de asma. La utilización de un punto de corte menor, de 8 por ciento a 10 por ciento, mejora significativamente la sensibilidad para el diagnóstico de asma en niños y podría considerarse en casos individuales, requiriéndose más estudios para recomendar su uso en niños. Una RBD positiva en niños se ha asociado con biomarcadores de inflamación, función pulmonar futura, respuesta a corticoides inhalatorios y pobre control del asma, por lo tanto podría entregar al médico una herramienta más para una mejor evaluación de los niños con asma sobre todo cuando su espirometría basal es normal.

Utility of bronchodilator response for asthma diagnosis in Latino preschoolers.

BACKGROUND: Asthma diagnosis in preschoolers is mostly based on clinical evidence, but a bronchodilator response could be used to help confirm the diagnosis. The objective of this study is to evaluate the utility of bronchodilator response for asthma diagnosis in preschoolers by using spirometry standardised for this specific age group. METHODS: A standardised spirometry was performed before and after 200 mcg of salbutamol in 64 asthmatics and 32 healthy control preschoolers in a case-control design study. RESULTS: The mean age of the population was 4.1 years (3-5.9 years) and 60% were females. Almost 95% of asthmatics and controls could perform an acceptable spirometry, but more asthmatics than controls reached forced expiratory volume in one second (FEV1) (57% vs. 23%, p=0.033), independent of age. Basal flows and FEV1 were significantly lower in asthmatics than in controls, but no difference was found between groups in forced vital capacity (FVC) and FEV in 0.5s (FEV0.5). Using receiver operating characteristic (ROC) curves, the variable with higher power to discriminate asthmatics from healthy controls was a bronchodilator response (% of change from basal above the coefficient of repeatability) of 25% in forced expiratory flow between 25% and 75% (FEF25₋75) with 41% sensitivity, 80% specificity. The higher positive likelihood ratio for asthma equalled three for a bronchodilator response of 11% in FEV0.5 (sensitivity 30%, specificity 90%). CONCLUSIONS: In this sample of Chilean preschoolers, spirometry had a very high performance and bronchodilator response was very specific but had low sensitivity to confirm asthma diagnosis.

Atopy, cytokine production, and airway reactivity as predictors of pre-school asthma and airway responsiveness.

BACKGROUND: Childhood asthma is often characterized by recurrent wheezing, airway hyper-reactivity, atopy, and altered immune characteristics; however, our understanding of the development of these relationships from early in life remains unclear. The aim of our study was to evaluate whether atopy, cytokine production by peripheral blood mononuclear cells (PBMCs), and airway responsiveness, assessed in infants and toddlers, are associated with asthma and airway responsiveness at 4-years of age. METHODS: Infants with eczema (N = 116), enrolled prior to wheezing, were assessed at entry (mean age of 10.7 months), at 1-year follow-up (N = 112), and at 4-years of age (N = 94). Total serum IgE, specific IgE to allergens, and cytokines produced by stimulated PBMCs, were assessed at entry and 1-year follow-up. Spirometry was obtained at all 3-visits, while airway reactivity to methacholine was assessed at entry and 1-year follow-up, and bronchodilator (BD) responsiveness, as well as current asthma was assessed at 4-years of age. RESULTS: We found that pre-school children with asthma had lower spirometry and a greater BD-response. Serum IgE, particularly to egg and/or milk, and altered cytokine production by PBMCs at entry to the study were associated with asthma, lower spirometry, and greater airway responsiveness at 4-years of age. In addition, we found that airway responsiveness, as well as spirometry, tracked from infancy to 4-years of age. CONCLUSIONS: While spirometry and airway responsiveness track longitudinally from early in life, atopy and cytokine production by PBMCs are associated not only with an increased risk of pre-school asthma, but also lower spirometry and increased airway responsiveness.