Clinical implications of having reduced mid forced expiratory flow rates (FEF25-75), independently of FEV1, in adult patients with asthma

INTRODUCTION:FEF25-75 is one of the standard results provided in spirometry reports; however, in adult asthmatics there is limited information on how this physiological measure relates to clinical or biological outcomes independently of the FEV1 or the FEV1/FVC ratio. PURPOSE:To determine the association between Hankinson's percent-predicted FEF25-75 (FEF25-75%) levels with changes in healthcare utilization, respiratory symptom frequency, and biomarkers of distal airway inflammation. METHODS:In participants enrolled in the Severe Asthma Research Program 1-2, we compared outcomes across FEF25-75% quartiles. Multivariable analyses were done to avoid confounding by demographic characteristics, FEV1, and the FEV1/FVC ratio. In a sensitivity analysis, we also compared outcomes across participants with FEF25-75% below the lower limit of normal (LLN) and FEV1/FVC above LLN. RESULTS:Subjects in the lowest FEF25-75% quartile had greater rates of healthcare utilization and higher exhaled nitric oxide and sputum eosinophils. In multivariable analysis, being in the lowest FEF25-75% quartile remained significantly associated with nocturnal symptoms (OR 3.0 [95%CI 1.3-6.9]), persistent symptoms (OR 3.3 [95%CI 1-11], ICU admission for asthma (3.7 [1.3-10.8]) and blood eosinophil % (0.18 [0.07, 0.29]). In the sensitivity analysis, those with FEF25-75% <LLN had significantly more nocturnal and persistent symptoms, emergency room visits, higher serum eosinophil levels and increased methacholine responsiveness. CONCLUSIONS:After controlling for demographic variables, FEV1 and FEV1/FVC, a reduced FEF25-75% is independently associated with previous ICU admission, persistent symptoms, nocturnal symptoms, blood eosinophilia and bronchial hyperreactivity. This suggests that in some asthmatics, a reduced FEF25-75% is an independent biomarker for more severe asthma

Clinical Implications of Serum Retinol-Binding Protein 4 in Asthmatic Children

Recently the prevalence of both asthma and obesity have increased substantially in many countries. The aim of this study was to evaluate the role of retinol-binding protein (RBP) 4 in childhood asthma and its association with atopy markers, pulmonary function, and bronchial hyperresponsiveness in relation to obesity. We studied 160 children between the ages 6 to 10 yr, including 122 asthmatics and 38 controls. The body mass index, pulmonary function tests, and methacholine challenge tests were measured on the same day. Total eosinophil count, serum total IgE, serum eosinophil cationic protein, and serum RBP4 were measured in all subjects. There was no difference in serum RBP4 levels between the asthmatics and the control group. In all subjects or subgroups, serum RBP4 was not associated with total eosinophil count, serum total IgE, serum eosinophil cationic protein, or PC20. There was no relationship between serum RBP4 and pulmonary function in female asthmatics. Forced expiratory volume in 1 second/forced vital capacity (FVC) and forced expiratory flow between 25% and 75% of FVC contributed to serum RBP4 in male asthmatics. Our findings show an association between RBP4 and pulmonary function in prepubertal male asthmatics. This relationship may indirectly affect the high prevalence of childhood asthma in males

A retrospective cohort study to evaluate the relationship of airway hyperresponsiveness to type 2 biomarkers in persistent asthma

Airway hyperresponsiveness (AHR) is a hallmark of persistent asthma measured using direct or indirect airway bronchial challenge testing. The purpose of this study is to investigate the putative relationships between type 2 inflammatory biomarkers, airway geometry (FEV1 and FEF25-75) and specific IgE (RAST or skin prick) to AHR. We performed a retrospective analysis of our database (n = 131) of patients with asthma. Of these subjects, 75 had a histamine challenge and 56 had a mannitol challenge. Fractional exhaled nitric oxide (FeNO) and specific immunoglobulin E (IgE) but not blood eosinophils were significantly higher in patients with AHR to either histamine or mannitol. FEV1 % and FEF25 - 75 % were significantly lower in patients with AHR. Elevated Type 2 biomarkers including FeNO and specific IgE but not blood eosinophils were associated with AHR. Highlights: FeNO and specific IgE but not blood eosinophils are raised in patients with airway hyperresponsiveness

Diagnosis of bronchial hyperresponsiveness in sport by PC20 value

En este trabajo se exponen los criterios de positividad del Comité Olímpico Internacional versus a la Sociedad Española de Neumología y Cirugía Torácica. Participaron en este estudio ochenta deportistas de alto rendimiento, realizando una historia clínica, una espirometría de reposo y un test de metacolina. Se analiza la sensibilidad y especificidad del test de metacolina mediante curvas ROC. El comité Internacional antidopaje (WADA) requiere que la disminución sea con un PC20 < a 4mg/ml, mientras que para la práctica clínica este descenso debe presentar un PC20 < 8mg/ml. Los resultados fueron: 25% tuvieron un PC20 > de 8mg/ml; el 61% obtuvieron un PC20 < 4mg/ml y un 14% presentaron un PC20 entre 4 y 8mg/ml, correspondiendo el mejor punto de corte a PC20 de 7,6mg/ml con especificidad de 98,3 y sensibilidad de 100%. Se tendría que determinar los mismos criterios para el diagnóstico de los deportistas y los que no lo son.In this work criteria of the International Olympic Committee versus the Spanish Society of Pneumology and Thoracic Surgery are exposed. A study was conducted in eighty high performance athletes of several sports . Who underwent a medical history, resting spirometry and a methacholine challenge test. You get the sensitivity and specificity of methacholine challenge test using Receiver Operating Curves (ROC curves). International anti-doping Committee requires that the decline is a PC20 < 4mg/ml, while clinical practice this fall must submit a PC20 < 8mg/ml. Twenty five percent of those studied had a PC20 > of 8mg/ml, 61% had a PC20 < 4mg/ml and 14% had a 4 to 8mg/ml PC20. The best cutoff point was found for a PC20 of 7.6 mg/ml with a specificity of 98.3 and a sensitivity of 100%. It would have to determine the same criteria for positive diagnosis of athletes and those who are not

Airway resistance at maximum inhalation as a marker of asthma and airway hyperresponsiveness

<p>Abstract</p> <p>Background</p> <p>Asthmatics exhibit reduced airway dilation at maximal inspiration, likely due to structural differences in airway walls and/or functional differences in airway smooth muscle, factors that may also increase airway responsiveness to bronchoconstricting stimuli. The goal of this study was to test the hypothesis that the minimal airway resistance achievable during a maximal inspiration (R_min) is abnormally elevated in subjects with airway hyperresponsiveness.</p> <p>Methods</p> <p>The R_minwas measured in 34 nonasthmatic and 35 asthmatic subjects using forced oscillations at 8 Hz. R_minand spirometric indices were measured before and after bronchodilation (albuterol) and bronchoconstriction (methacholine). A preliminary study of 84 healthy subjects first established height dependence of baseline R_minvalues.</p> <p>Results</p> <p>Asthmatics had a higher baseline R_min% predicted than nonasthmatic subjects (134 ± 33 vs. 109 ± 19 % predicted, p = 0.0004). Sensitivity-specificity analysis using receiver operating characteristic curves indicated that baseline R_minwas able to identify subjects with airway hyperresponsiveness (PC₂₀< 16 mg/mL) better than most spirometric indices (Area under curve = 0.85, 0.78, and 0.87 for R_min% predicted, FEV₁% predicted, and FEF_25-75% predicted, respectively). Also, 80% of the subjects with baseline R_min< 100% predicted did not have airway hyperresponsiveness while 100% of subjects with R_min> 145% predicted had hyperresponsive airways, regardless of clinical classification as asthmatic or nonasthmatic.</p> <p>Conclusions</p> <p>These findings suggest that baseline R_min, a measurement that is easier to perform than spirometry, performs as well as or better than standard spirometric indices in distinguishing subjects with airway hyperresponsiveness from those without hyperresponsive airways. The relationship of baseline R_minto asthma and airway hyperresponsiveness likely reflects a causal relation between conditions that stiffen airway walls and hyperresponsiveness. In conjunction with symptom history, R_mincould provide a clinically useful tool for assessing asthma and monitoring response to treatment.</p

Forced expiratory flow between 25% and 75% of vital capacity as a predictor for bronchial hyperresponsiveness in children with allergic rhinitis

Purpose Allergic rhinitis (AR) is regarded as a risk factor for asthma and bronchial hyperresponsiveness (BHR) is frequently observed in patients with AR. The purpose of this study is to analyze the characteristics of AR patients with BHR and identify factors that contribute to the incidence of BHR. Methods The medical records of a total of 176 children with AR were analyzed retrospectively. All patients were evaluated by performing spirometry and a methacholine challenge test. Results One hundred and fifty-five patients (88%) were classified as the BHR-negative group and 21 patients (12%) were classified as the BHR-positive group. Forced expiratory flow between 25% and 75% of vital capacity (FEF25-75 %predicted) was reduced, and total eosinphil counts, total immunoglobulin E (IgE) level, and serum specific IgE levels of Dermatophagoides pteronyssinus and Dermatophagoides farinae were higher in the BHR-positive group compared to the BHR-negative group. However, FEF25-75 was the only statistically significant predictor for the presence of BHR on multivariate logistic regression analysis. The cutoff value to distinguish BHR-positive subjects obtained from a receiver operating characteristics curve of FEF25-75 was 88.4%. A higher frequency of BHR was found in the group with a FEF25-75 less than 88.4%, and the sensitivity, specificity, positive predictive value and negative predictive value were 57.1%, 80.6%, 28.6%, and 93.3%, respectively. Conclusion Reduced FEF25-75 values in children with AR can be helpful in predicting BHR. Children with low FEF25-75 in spirometric tests should be followed closely for apparent onset of clinical symptoms of asthma.ope

Increased B cell-activating factor (BAFF) level in the sputum of children with asthma

PurposeB cell-activating factor (BAFF) is a tumor-necrosis factor (TNF) superfamily member best known for its role in the survival and maturation of B cells. BAFF activity is observed in naïve cells as well as in effector/memory T cells. We aimed to explore whether BAFF in sputum is expressed at elevated levels in asthmatic airways and associated with eosinophilic inflammation, pulmonary function, and bronchial hyperresponsiveness in children.MethodsOne hundred and fifty-four asthmatic children and 98 healthy children were enrolled in the study. Sputum supernatants were collected and sputum BAFF and eosinophil cationic protein (ECP) levels were measured. We performed pulmonary function tests and methacholine challenge tests, while measuring total eosinophil count, total serum IgE, and serum ECP in all subjects.ResultsAsthmatic children had significantly higher levels of BAFF in induced sputum [26.50 (10.50-100.27) pg/mL] compared to healthy children [18.32 (7.68-44.63) pg/mL; P=0.011]. Sputum BAFF positively correlated with sputum eosinophils (γ=0.406, P<0.001) and sputum ECP (γ=0.789, P<0.001). Significant negative correlations were found between sputum BAFF and FEV1 (γ=-0.291, P<0.001) or post-bronchodilator FEV1 (γ=-0.334, P<0.001), whereas nonsignificant correlations were found between sputum BAFF and bronchial hyperresponsiveness, serum eosinophil count, and serum ECP.ConclusionThese findings suggest that BAFF may play a role in childhood asthma, and BAFF levels in sputum could be a supportive marker that represents airway inflammation, especially eosinophilic inflammation