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Bronchodilator response as a marker of poor asthma control
... Bronchodilator response (BDR) is an important method for diagnosing airway reversibility, which is primarily observed in asthma but may also be observed in COPD [2][3][4]. It is significant in asthma because it reflects poor control of the disease; however, its clinical significance in COPD is not clear [5,6]. ...
... Although BDR is associated with worse control of disease and frequent use of reliever medications in asthmatic patients [5,6], it is not associated with the risk for COPD exacerbations [7,8,10,11,13]. In the ECLIPSE study, although the exacerbation rate was significantly higher in patients with less reversible than more reversible airway restriction, the results may have been affected by the lack of adjustment for baseline FEV1 [8,28]. ...
Background:
The clinical implication of bronchodilator response (BDR) is not fully understood. However, BDR is frequently present in patients with chronic obstructive pulmonary disease (COPD). We identified the differences in clinical features regarding BDR. In addition, we divided BDR into BDR for forced expiratory volume in 1 s (FEV1) and BDR for forced vital capacity (FVC; i.e., BDR-FEV1 and BDR-FVC, respectively) and analyzed clinical significance.
Methods:
We used data from the Korea COPD Subgroup Study, a multicenter cohort study of COPD patients recruited from 54 centers in South Korea since April 2012. We analyzed differences in baseline characteristics, 1-year exacerbation rate, and 3-year FEV1 decline between BDR negative and positive patients. Moreover, we analyzed the differences in clinical features between BDR-FEV1 positive and negative patients and between BDR-FVC positive and negative patients.
Results:
Of the 2,181 patients enrolled in this study, 366 (16.8%) were BDR positive. BDR positive patients were more likely to be ever-smokers and to have a lower body mass index and higher symptom scores compared to BDR negative patients. Baseline FEV1 and FEV1/FVC were lower in the BDR positive compared to the BDR negative group (1.7 ± 0.6 and 1.6 ± 0.5, respectively, p < 0.01; 50.9 ± 12.1 and 46.5 ± 14.8, respectively, p < 0.01). BDR positive patients were more likely to have been diagnosed with asthma-COPD overlap and to receive inhaled corticosteroids (ICS) than BDR negative patients. BDR-FVC patients were more likely to be smokers, suffer from worse symptoms and have lower lung function than those with no BDR-FVC. BDR had no significant effect on 1-year moderate to severe or severe exacerbation rates or 3-year annual FEV1 decline. Interactive effects of ICS and BDR on the exacerbation rate were not significant in any group.
Conclusions:
In this study, BDR positive patients were more likely to be ever-smokers and to have worse symptoms and lung function than BDR negative patients. BDR-FVC was associated with worse symptom control and lung function compared to BDR-FEV1. However, there were no significant differences in exacerbation rate or decline in lung function in any BDR group. In addition, the effects of ICS on exacerbations were not significant in any group.
... 15 Uncontrolled asthma was defined as an increase of at least 12% of the forced expiratory volume in 1-second (FEV1) after bronchodilation test or respiratory symptoms in the previous weeks with exhaled NO levels higher than 35 ppb. 16 The control group was composed by all included participants who do not meet the asthma group inclusion criteria. ...
... During asthma management the presence of airway reversibility does not support stepping down treatment, which would be done if disease was under control. Also, a recent study by Heffler and colleagues showed bronchodilator response to be a marker of poor controlled asthma.16 F I G U R E 2 Receiver operating characteristic (ROC) curves for asthma control using: (A) absolute exhaled NO values (AUC = 0.707, P = .011); ...
Spirometry and exhaled nitric oxide are two important complimentary tools to identify and assess asthma control in children. We aimed to determine the ability of a new suggested spirometry adjusted exhaled nitric oxide (NO) index in doing that. A random sample of 1602 schoolchildren were screened by a health questionnaire, skin-prick tests, spirometry with bronchodilation and exhaled NO. A total of 662 children were included with median (IQR) exhaled NO 11(14) ppb. ROC curves using exhaled NO equations from Malmberg, Kovesi and Buchvald, and spirometry adjusted exhaled NO values were applied to identify asthmatic children and uncontrolled asthma. ROC curves failed to identify asthmatic children (all AUC<0.700). Spirometry adjusted exhaled NO/FEV1 (AUC=0.712; p=0.010) and NO/FEF25-75% (AUC=0.735 p=0.004) had a fair and increased ability to identify uncontrolled disease compared with exhaled NO (AUC=0.707; p=0.011) or the Malmberg equation (AUC=0.701; p=0.014). Sensitivity and specificity identifying non-controlled asthma was of 59% and 81%, respectively, for the cut-off value of 9.7 ppb/L for exhaled NO/FEV1 , and 40% and 100% for 15.7 ppb/L/s for exhaled NO/FEF25-75% . Exhaled NO did not allow to identify childhood asthma. Spirometry adjusted fraction of exhaled NO performed better assessing asthma control in children. Thus, despite more validation studies are needed, we suggest its use in epidemiological studies to assess asthma control.
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© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.
... It suggests that even in the case of milder asthma forms, a further improvement can be achieved during dupilumab treatment course. After all, it is known that even in the presence of normal lung function parameters, significant post-bronchodilator reversibility can be detected in asthma patients [29] and that persistent bronchodilator response in treated asthma patients correlates with lower disease control [30]. Similar findings were reported by Minagawa et al. [12], who conducted a study on 62 CRSwNP patients, 50 of them with comorbid mild-to-moderate asthma and 12 with severe asthma. ...
Dupilumab is currently approved for the treatment of Type 2 severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). Few studies have specifically reported on dupilumab efficacy on asthma outcomes as a primary objective in a real-life setting, in patients with and without CRSwNP. Our study aimed to explore the efficacy of dupilumab on functional, inflammatory, and patient-reported outcomes in asthma patients across different disease phenotypes and severity, including mild-to-moderate asthma coexisting with CRSwNP. Data from 3, 6, and 12 months follow-up were analyzed. Asthma (FEV1%, Tiffeneau%, ACT, FeNO, oral steroid use, exacerbation rate, and blood eosinophilia) and polyposis (SNOT22, VAS, NPS) outcomes showed a rapid (3 months) and sustained (6 and 12 months) significant change from baseline, despite most of the patients achieving oral steroid withdrawal. According to the sensitivity analysis, the improvement was not conditioned by either the presence of polyposis or severity of asthma at baseline. Of note, even in the case of milder asthma forms, a significant further improvement was recorded during dupilumab treatment course. Our report provides short-, medium-, and long-term follow-up data on asthma outcomes across different diseases phenotypes and severity, contributing to the real-world evidence related to dupilumab efficacy on upper and lower airways T2 inflammation.
... 2,5 Besides its diagnostic purpose, the persistence of BDR is a marker of poor asthma control and predictive of a good response to inhaled corticosteroids (ICS). 12,13 Previous studies have reported evidence of airway reversibility in children with asthma with good asthma control or normal lung function. 14,15 These controversial findings affect the role of spirometry and BDR testing in asthma management. ...
Purpose
It is still unclear whether considering abnormal spirometry as a marker for disease control can help physicians adjust asthma controllers in children because of the scarcity of pediatric studies. We aimed to investigate the prevalence of abnormal spirometry in a selected pediatric asthmatic population and its effect on longitudinal outcomes.
Patients and Methods
This retrospective cohort study was conducted at the Songklanagarind Hospital, Thailand. Children with asthma aged <18 years were recruited for review if they attended the clinic and underwent acceptable spirometry with bronchodilator responsiveness (BDR) tests after receiving asthma treatment for at least 3 months between January 2011 and June 2022. Differences in baseline characteristics, atopic factors, asthma treatment, and outcomes were analyzed between the normal and abnormal spirometry groups over a 12-month post-spirometry period.
Results
The mean age of the 203 enrolled patients was 10.9 ± 2.6 years. Abnormal spirometry, defined as airflow limitation or the presence of BDR, was observed in 58.1% of patients. No significant differences were observed in baseline characteristics, atopic factors, asthma treatment, or outcomes between the normal and abnormal spirometry groups. Further analysis of 107 patients with abnormal spirometry with symptom control revealed that physicians adjusted the asthma controller based on spirometry and symptoms in 84 and 23 patients, respectively. There was no significant difference in the loss of disease control over the 12-month post-spirometry period between the two groups.
Conclusion
Abnormal spirometry was found in 58.1% of treated school-aged patients with asthma. Abnormal spirometry results were not associated with poor asthma outcomes during the 12-month follow-up. Both symptom-based and spirometry-based adjustments of asthma controllers resulted in comparable symptom control over a 12-month follow-up period in the selected population.
... Their persistence of symptoms may reflect poor bronchodilator response that correlates to worse asthma control in a patient even with normal spirometry; such cases need a bronchodilator responsiveness test that provides useful information. [7] At the first encounter, a physician at a secondary or tertiary care level finds it difficult or even impossible at times to withdraw the medicines for even a day or so. Therefore, the physician often tends to advise spirometry and bronchial responsiveness on the same day after the initial consultation and intends to offer a prescription based on the best possible pragmatic assessment. ...
... BR, including the bronchial dilation test (BDT) and bronchodilator-dose responsiveness (BDR), 26 can also predict future exacerbation of asthma in children or adolescents. [26][27][28] The basis of BR is the natural state of ASM, which is determined by both inherent properties of ASM and external factors as mentioned before, and that may also lead to some difference compared to PRI: First, BR and inflammation factors present a certain degree of positive correlation. The related inflammation factors include sensitization to aeroallergen, serum IgE, reactivity on a skin test, EOS 27 and FENO (present large airway inflammation). ...
Background:
Previous studies indicate that the percent recovery index (PRI: the percentage increase from the maximally reduced FEV1 after bronchodilator inhalation), one of the indexes of methacholine bronchial provocation, may predict acute asthma exacerbations in childhood and elderly asthmatics. It is known that childhood (<12) and elder (>60) asthmatics may be different to adult patients in many aspect including prognosis. However, in adults, a research for predicting value of PRI to exacerbation is still absence. Besides exacerbation, predicting value of PRI to poor asthma control is also unknown. We try to detect whether PRI can predict poor asthma control and exacerbation in adults in this research. Meanwhile, we try to detect whether treatment can influence PRI.
Methods:
In 61 adults with asthma, baseline PRI was measured during enrollment. And then baseline PRI was evaluated as a predictor of exacerbation or poor asthma control at an upcoming 3-month follow-up. The covariates included age, sex, BMI, previous exacerbation, smoking status and baseline lung function. After treatment for 3 months, PRI was measured again and compared with baseline PRI.
Results:
After the 3-month follow-up, we found that baseline PRI was significantly related to asthma exacerbation (P = 0.023), poor asthma control (ACT at 3 months, P = 0.014), decreased quality of life (decrease of MiniAQLQ, P = 0.010) and cumulative number of EDHO at 3 months (P = 0.039). Meanwhile, no significant correlation was observed between baseline PRI and inflammation factors (FENO, CaNO, and EOS). Finally, PRI was dramatically reduced after standard treatment for 3 months.
Conclusion:
PRI is efficient in the prediction of poor asthma control and exacerbation in adults. The predictive value of PRI may rely on the inherent property of asthmatic airway smooth muscle (ASM) independent of inflammation factors. Effective treatment can alleviate PRI dramatically and that indicate PRI may also be valuable in evaluation of curative effect.
... Furthermore, the present study showed the elderly patients had significantly higher bronchodilator response of FEV₁ and FVC than the non-elderly patients. Previous studies of Bauer et al (24) and Heffler et al (25) found that higher bronchodilator reversibility indicated worse asthma control. Unlike younger patients with asthma, most elderly patients show incomplete reversibility (5) . ...
Background: Asthma in the elderly is underdiagnosed and associated with a higher risk for morbidity and mortality.
Objective: To describe clinical features and lung functions of asthma in Thai elderly patients.
Materials and Methods: The authors extracted data from the electronic medical records at Thammasat University Hospital between 2015 and 2019. Asthmatic patients aged 18 years or older were included and divided into elderly, being 65 years or older and non-elderly groups being younger than 65 years.
Results: Two thousand three hundred ninety-nine patients were screened and 1,600 were eligible for the study with 72.6% female. The median (IQR) age was 54.0 years (44.0, 64.0). FEV₁ was 74.6% (61.3, 86.7). There were 410 patients (25.6%) in the elderly group, or a prevalence of 0.23% of all elderly patients. Compared to the non-elderly group, patients in the elderly group were more predominantly female, had lower prevalence of allergic rhinitis, but higher prevalence of hypertension and diabetes. The elderly group also had lower pre-bronchodilator FVC at 77.2% (62.1, 91.8) versus 81.2% (69.8, 91.6) (p=0.012), and pre-bronchodilator FEV₁ of 1.23 L (0.96, 1.53) versus 1.86 L (1.42, 2.34) (p<0.001). Only bronchodilator response in FVC was higher in the elderly group, compared to the non-elderly group at 9.2% (2.7, 17.1) versus 3.9% (0.0, 10.4) (p<0.001).
Conclusion: Asthma prevalence in Thai elderly patients at a university hospital was low. Elderlies with asthma had lower prevalence of allergic rhinitis, lower lung functions, but higher bronchodilator response compared to non-elderly patients. Future studies should investigate the effects of comorbid diseases and lung functions on asthmatic outcomes among elderly patients.
Keywords: Asthma; Elderly; Lung functions; Prevalence
... BDR, for example, is a marker of airway lability and is associated with poor asthma control 30 . Nearly 30% of children in our lowest adherence quartile showed BDR > 12%, more than in the highest adherence quartile (p = 0.055). ...
Poor adherence to asthma preventer medication is associated with life-threatening asthma attacks. The quality and outcomes framework mandated primary care annual asthma review does not include adherence monitoring and the effect of poor adherence on lung function in paediatric primary care patients is unknown. The aim was to investigate the link between inhaled corticosteroid (ICS) adherence and spirometry, fraction of exhaled nitric oxide (FeNO) and asthma control in asthmatic school-age children in this cross-sectional observational study involving three Leicestershire general practices. Children 5–16 years on the practice’s asthma registers, were invited for a routine annual asthma review between August 2018 and August 2019. Prescription and clinical data were extracted from practice databases. Spirometry, bronchodilator reversibility (BDR) and FeNO testing were performed as part of the review. 130 of 205 eligible children (63.4%) attended their review. Mean adherence to ICS was 36.2% (SEM 2.1%) and only 14.6% of children had good adherence (≥75% prescriptions issued). We found no differences in asthma exacerbations in the preceding 12 months between the adherence quartiles. 28.6% of children in the lowest and 5.6% in the highest adherence quartile had BDR ≥ 12% but this was not statistically significant ( p = 0.55). A single high FeNO value did not predict adherence to ICS. Adherence to ICS in children with asthma in primary care is poor. The link between adherence to ICS and asthma exacerbations, spirometry and FeNO is complex but knowledge of adherence to ICS is critical in the management of children with asthma.
... We also found that in patients with positive BDR, PFT parameters showed more severe obstructive defects at baseline. Also, Heffler et al showed that positive BDR is a marker of poor asthma control even when BDR testing was performed without pausing asthma medications except for LABAs [32]. ...
Background and objective:
Positive bronchodilator reversibility (BDR) is a diagnostic criterion for asthma. However, patients with asthma may exhibit negative BDR test.To describe frequency of positive and negative BDR in patients with severe asthma and associations with phenotypic characteristics.
Methods:
Positive BDR was defined as FEV1 increase > 200 ml AND > 12% upon testing with a short-acting beta-agonist (SABA).
Results:
Out of 2013 patients included in the German Asthma Net (GAN) severe asthma registry, 793 had data on BDR. Hereof, 250 (31.5%) had a positive and 543 (68.5%) had a negative BDR test. Comorbidities significantly associated with negative BDR were gastro-esophageal reflux (GERD) (28.0% vs 40.0%, p<0.01) and EGPA (0.4% vs 3.0%; p<0.05), while smoking history (active: 2.8% vs 2.2%; ex: 40.0% vs 41.7%) and COPD comorbidity (5.2% vs 7.2%) were similar in both groups. Patients with positive BDR had worse asthma control (median ACQ-5 3.4 vs 3.0, p<0.05), reported dyspnea at rest (26.8% vs 16.4%, p<0.001) and chest tightness (36.4% vs 26.2%, p<0.001) more frequently, had more severe airway obstruction at baseline (FEV1% pred: 56 vs 64, p<0.001) and higher FeNO levels (41 vs 33 ppb, p<0.05), while diffusion capacity did not differ (DLCO-SB % pred. 70% vs 71%). Multivariate linear regression analysis identified association of lower baseline FEV1% (p<0.001) and chest tightness (p<0.05) with positive, and GERD (p<0.05) with negative BDR.
Conclusion:
In this real-life setting the majority of patients with severe asthma exhibited negative BDR. Interestingly, this was not associated with smoking history or COPD, but with lower FeNO and presence of GERD.
... No relationship was found between asthma control status and other lung function indices during the study period. This result mirrors that of a recent study conducted in adult asthmatic patients in which significant bronchodilation was related to poor asthma control independently of the presence of baseline bronchial obstruction (10). Interestingly, the decrease in exacerbation rate after the first reopening corresponded to the period when children went back to school (September 2020). ...
Introduction: Little is known on the effect of SARS-CoV-2 circulation on asthma daily symptoms in children. We compared asthma exacerbations, asthma symptom control and lung function before and after SARS-CoV-2 outbreak in children.
Methods: Retrospective study of children with persistent asthma referred for lung function testing. The second quarter of 2020 being a period with nearly no activity, we compared the activity between the first, third and fourth quarters of 2019 and 2020 (Q1-2019 vs. Q1-2020, Q3-2019 vs. Q3-2020 and Q4-2019 vs. Q4-2020).
Results: We retrieved 1,871 files in 2019 and 1,548 in 2020. The whole population [2,165 (63.3%) boys] had a median [IQR] age of 9.7 [6.8;13.1] years. There was no difference in age, sex, and ethnicity between 2019 and 2020 populations. Asthma was better controlled during Q4-2020 compared to Q4-2019 ( P = 0.042), and there was a lower proportion of children with at least one exacerbation in the previous 3 months after the reopening, compared to the same period in 2019 ( P < 0.0001). Baseline FEV 1 (Z-score) recorded after the reopening was significantly higher (with less reversibility) compared to the same period before the epidemic ( P < 0.0001). Baseline FEV 1 /FVC (Z-score) was significantly higher during Q3-2020 compared to Q3-2019 ( P = 0.026), with fewer children having a significant reversibility ( P = 0.035).
Discussion: We demonstrated a trend toward increased exacerbations just before the recognition of the epidemic, and fewer exacerbations, better asthma symptom control and improvement in the lung function of asthmatic children after the reopening.
... En un estudio reciente en 246 asmáticos adultos con tratamiento de mantenimiento, seguidos durante un año demostró que existe correlación entre la prueba broncodilatadora y el Asthma control Test (ACT), a mayor resultado en la prueba broncodilatadora menor puntuación en el ACT. (29) Los resultados coinciden significativamente con estudio realizado por Sánchez, donde evaluó 99 pacientes con asma, clasificándolos por IMC, y posterior realización de prueba broncodilatadora, llegando a la conclusión que la RAB disminuye significativamente a medida que aumenta el IMC en pacientes asmáticos. (27) El asma es más frecuente en pacientes obesos que en los no obesos, más difícil de controlar, esto puede deberse a un tipo diferente de inflamación de las vías aéreas, a comorbilidades que contribuyan a ella, a factores mecánicos o a otros factores todavía no definidos, además la mala forma física y la reducción del volumen pulmonar a causa de la grasa abdominal pueden contribuir a producir disnea. ...
Introducción:
La obesidad está asociada al uso frecuente de medicación de rescate y padecer asma de mayor gravedad. Los obesos asmáticos tienen menor reactividad bronquial, sin embargo, existe información limitada sobre la magnitud de la reversibilidad aguda al broncodilatador (RAB).
Objetivo:
Evaluar la magnitud de respuesta aguda al broncodilatador en pacientes asmáticos sobrepesos y obesos.
Métodos:
Se realizó un estudio descriptivo transversal con 49 pacientes asmáticos sobrepesos y obesos atendidos en consulta externa del Hospital Neumológico Benéfico Jurídico (enero 2017˗ enero 2018) y se constató mediante espirometría la respuesta aguda al broncodilatador.
Resultados:
Predominó la edad (40-59 años), mayor asociación de padecer asma, poca mejoría con la aplicación del broncodilatador. El sexo femenino (20-59 años) presentó mayor número que el masculino y menor reversibilidad al broncodilatador. Los pacientes con antecedentes patológicos familiares de asma o atopia representaron 73,5 % del total. El 76,5 % de los obesos no presentó mejoría con la aplicación del broncodilatador. Predominó la categoría de gravedad persistente moderada.
Conclusiones:
El sexo femenino tiene más riesgo de padecer asma y no tener mejoría al aplicar el broncodilatador. Los obesos mayores de 40 años tienen mayor riesgo de no presentar reversibilidad aguda al broncodilatador. Los antecedentes patológicos familiares de asma o atopia y personales de otras enfermedades no predisponen a menor reversibilidad aguda al broncodilatador. La gravedad del asma no influye en la reversibilidad aguda al broncodilatador.
... The ACQ age and administration versions fitted perfectly with the inclusion criteria of the ARCA study, where it is administered by telephone interview to all participants, as some age groups require trained interviewer administration. The Asthma Control Test (ACT) [50] was included in more articles of the review (13 studies [48,49,[51][52][53][54][55][56][57][58][59][60][61]), but it was designed for patients older than 12 years. ...
Purpose
The asthma stepwise treatment approach recommended is based on monitoring patients’ symptoms. The Asthma Research in Children and Adolescents (ARCA) cohort was created to provide evidence about the evolution of persistent asthma. This manuscript describes the development of an electronic health tool, comprising a mobile health application for patients with asthma and its associated online platform for pediatricians to monitor them.
Methods
The development process followed 7 phases: the first 5 (Conceptualization, Preparation, Assessment scheduling, Image and user interface, and Technical development) defined and designed the tool, followed by a testing phase (functionality assessment and pilot test with ARCA patients), and a last phase which evaluated usability. Since the target population was aged 6–16 years, three versions were designed within the same smartphone application: parents/proxy, children, and adolescents. The online platform for pediatricians provides real-time information from the application: patients’ responses over time with color-coded charts (red/amber/green, as in traffic lights).
Results
The pilot test through semi-structured phone interviews of the first 50 participants included in the ARCA study (n = 53) detected their misunderstandings. Pediatricians were trained to emphasize that the application is free of charge and requires monthly answers. Median of the System Usability Scale scores (n = 85), ranging 0 (negative)–100 (positive), was > 93 in the three age versions of the application.
Conclusions
Technology has the capability of transforming the use of patient-reported outcomes. Describing all the development phases of a mobile health application for monitoring children and adolescents with asthma may increase the knowledge on how to design applications for young patients.
... Furthermore, a persistent BDR despite anti-inflammatory treatment has been associated with greater inhaled corticosteroid doses, lower FEV1, worse asthma control, and higher exacerbation rates. 37,38 Therefore, we postulated that TRPM8 is a candidate molecular marker associated with the physiologic response and poor outcomes in asthmatic patients. ...
Purpose:
Cold air is a major environmental factor that exacerbates asthma. Transient receptor potential melastatin family member 8 (TRPM8) is a cold-sensing channel expressed in the airway epithelium. However, its role in airway inflammation remains unknown. We investigated the role of TRPM8 in innate immune responses in bronchial epithelial cells and asthmatic subjects.
Methods:
The TRPM8 mRNA and protein expression on BEAS2B human bronchial epithelial cells was examined by real-time polymerase chain reaction (PCR), immunofluorescence staining and western blotting. Additionally, interleukin (IL)-4, IL-6, IL-8, IL-13, IL-25 and thymic stromal lymphopoietin (TSLP) levels before and after menthol, dexamethasone and N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl) piperazine-1-carboxamide (BCTC) treatments were measured via real-time PCR. TRPM8 protein levels in the supernatants of induced sputum from asthmatic subjects and normal control subjects were measured using enzyme-linked immunosorbent assay, and mRNA levels in sputum cell lysates were measured using real-time PCR.
Results:
Treatment with up to 2 mM menthol dose-dependently increased TRPM8 mRNA and protein in BEAS2B cells compared to untreated cells (P < 0.001) and concomitantly increased IL-25 and TSLP mRNA (P < 0.05), but not IL-33 mRNA. BCTC (10 μM) significantly abolished menthol-induced up-regulation of TRPM8 mRNA and protein and IL-25 and TSLP mRNA (P < 0.01). TRPM8 protein levels were higher in the supernatants of induced sputum from asthmatic subjects (n = 107) than in those from healthy controls (n = 19) (P < 0.001), and IL-25, TSLP and IL-33 mRNA levels were concomitantly increased (P < 0.001). Additionally, TRPM8 mRNA levels correlated strongly with those of IL-25 and TSLP (P < 0.001), and TRPM8 protein levels were significantly higher in bronchodilator-responsive asthmatic subjects than in nonresponders.
Conclusions:
TRPM8 may be involved in the airway epithelial cell innate immune response and a molecular target for the treatment of asthma.
... Indeed, high reversibility has been shown to be a physiologic indicator of reduced lung function and is more often associated with elevated T H 2 levels in moderate to severe asthma. 35,36 Bronchial reversibility is also significantly correlated with worse asthma control 37 and is a distinguishing factor for difficult-to-control asthma in children and adolescents. 38 Longitudinal lung function trajectories in those with severe asthma can be used as potential indicators of reduced lung function and early decline; these trajectories may identify a subset of patients who have worse prognosis, such as those with structural changes linked to irreversible airway obstruction. ...
Background
Severe/difficult-to-treat disease occurs in 5–10% of asthma patients, but accounts for >50% of related economic costs. Understanding factors associated with persistent very poorly controlled (VPC) asthma may improve outcomes.
Objective
To characterize persistent VPC asthma after >10 years of standard of care.
Methods
TENOR II (N=341) was a multicenter, observational study of severe/difficult-to-treat asthma patients with a single, cross-sectional visit >10 years after TENOR I. Persistent VPC asthma was defined as VPC asthma at TENOR I and TENOR II enrollment; without VPC asthma was defined as well or not well controlled asthma at either or both visits. Multivariable logistic regression assessed long-term predictors of persistent VPC asthma using TENOR I baseline variables.
Results
Of 327 patients, nearly half (48.0%, n=157) had persistent VPC asthma. Comorbidities and asthma triggers were more frequent in persistent VPC than without VPC asthma patients. Total geometric mean IgE was higher in persistent VPC patients [89.3 IU/mL versus 55.7 IU/mL]; there was no difference in eosinophil levels. Lung function was lower in persistent VPC patients (mean % predicted pre- and post-bronchodilator FEV1: 63.0% versus 82.8% and 69.6% versus 87.2%, respectively). Exacerbations in the prior year were more likely in persistent VPC patients (29.7% versus 9.0%, respectively). Predictors of persistent VPC asthma were black versus white race/ethnicity, allergic trigger count (4 versus 0), systemic corticosteroid use, and post-bronchodilator FEV1 (per 10% decrease).
Conclusion
The burden of persistent VPC asthma is high in severe/difficult-to-treat disease; management of modifiable risk factors, maximization of lung function, and trigger avoidance may improve outcomes.
... A previous study with FOT revealed that the value of R5 could effectively predict asthma exacerbation in children [11]. Bronchodilator response was shown to be a marker of poor asthma control in adolescent and adult asthmatic patients [12,13]. The higher bronchodilator response as a risk factor for exacerbations was also documented in a recent GINA guideline [1]. ...
Background:
A reliable objective tool using as a predictor of asthma control status could assist asthma management.
Objective:
To find the parameters of forced oscillation technique (FOT) as predictors for the future loss of asthma symptom control.
Methods:
Children with well-controlled asthma symptom, aged 6-12 years, were recruited for a 12-week prospective study. FOT and spirometer measures and their bronchodilator response were evaluated at baseline. The level of asthma symptom control was evaluated according to Global Initiative for Asthma.
Results:
Among 68 recruited children, 41 children (60.3%) maintain their asthma control between 2 visits (group C-C), and 27 children (39.7%) lost their asthma control on the follow-up visit (group C-LC). Baseline FOT parameters, including the values of respiratory resistance at 5 Hz (R5), respiratory resistance at 20 Hz (R20), respiratory reactance at 5 Hz, area of reactance, %predicted of R5 and percentage of bronchodilator response (%∆) of R5 and R20 were significantly different between C-C and C-LC groups. In contrast, only %∆ of forced vital capacity, forced expiratory volume in 1 second (FEV1), and FEF25%-75% (forced expiratory flow 25%-75%) were significantly different between groups. Multiple logistic regression analysis revealed that %predicted of R5, %∆R5, %predicted of FEV1 and %∆FEV1 were the predictive factors for predicting the future loss of asthma control. The following cutoff values demonstrated the best sensitivity and specificity for predicting loss of asthma control: %predicted of R5=91.28, %∆R5=21.2, %predicted of FEV1=89.5, and %∆FEV1=7.8. The combination of these parameters predicted the risk of loss of asthma control with area under the curve of 0.924, accuracy of 83.8%.
Conclusion:
Resistance FOT measures have an additive role to spirometric parameter in predicting future loss of asthma control.
... A second hypothesis, contrary to our case-control findings, is that English language preference results in improved asthma control manifesting as decreased bronchodilator response (already at personal best) 64 and greater FEV 1 compared with that in children with low language acculturation. This is consistent with previous studies demonstrating that high language concurrence with a medical provider results in improved asthma control in Latinos. ...
Background
Acculturation is an important predictor of asthma in Latino youth, specifically Mexican Americans. Less is known about acculturation and pulmonary function measures.
Objective
We sought to estimate the association of acculturation measures with asthma and pulmonary function in Latino youth and determine whether this association varies across Latino subgroups.
Methods
We included 1849 Latinos (302 Caribbean Spanish, 193 Central or South Americans, 1136 Mexican Americans, and 218 other Latino children) aged 8 to 21 years from 4 urban regions in the United States. Acculturation measures include nativity status, age of immigration, language of preference, and generation in the United States. We used multivariable logistic and linear regression models to quantify the association of acculturation factors with the presence of asthma (case-control study) and pulmonary function (case-only study), adjusting for demographic, socioenvironmental, and clinical variables.
Results
For all acculturation measures (nativity status, age of immigration, language of preference, and generation in the United States), greater levels of acculturation were associated with greater odds of asthma. Among cases, high (English preference) and medium (equal preference for Spanish and English) levels of language acculturation were associated with decreased bronchodilator response compared with low (Spanish preference) levels (P = .009 and .02, respectively). Similarly, high language acculturation was associated with increased FEV1 compared with low language acculturation (P = .02). There was insufficient evidence of heterogeneity for associations across Latino subgroups.
Conclusions
Acculturation was associated with diagnosed asthma and pulmonary function in Latino children and is an important factor to consider in the management of Latino youth with asthma.
... As showed in other cohorts of patients 19,20 , in our study the FAO phenotype was not necessarily associated with more asthma symptoms, but a slightly increased prevalence of hospitalizations in the last year that deserves some mention. In contrast, in the RAO phenotype there was a stronger sIgE response to D. pteronyssinus and a tendency to more symptoms as described in other studies 17,59,60 , but a lower prevalence of hospitalizations, possibly those two different phenotypes of airway obstruction reflects two different clinical patterns of asthma. Smoking habit and exposure to cigarrete smoke can be aggravating factors, but they are not the only necessary condition for fixed airway obstruction outcome to occur in long lasting asthmatics 61 . ...
Microbiome composition has been associated to several inflammatory diseases, including asthma. There are few studies exploring the relationships of gut microbiota with airway obstruction pheonotypes in adult asthma, especially those living in the tropics. We sought to evaluate the relationships of gut microbiota with the airway obstruction and other variables of interest in asthmatic patients living in the tropics according to three phenotypes: No Airway Obstruction (NAO), Reversible Airway Obstruction (RAO) or Fixed Airway Obstruction (FAO). We found that Streptococcaceae:Streptococcus and Enterobacteriaceae:Escherichia-Shigella consistently discriminated asthmatic individuals suffering FAO from NAO or RAO, plus Veillonellaceae:Megasphaera when comparing FAO and RAO (p < 0.05; FDR < 0.05). In the FAO, the network showing the genus relations was less complex and interconnected. Several Rumminococcaceae, Lachnospiraceae and Clostridiales were enriched in patients with low specific IgE levels to mites and Ascaris. All patients shared a common exposure framework; control medication usage and smoking habit were uncommon and equally distributed between them. In conclusion, in this tropical asthmatic population, components of human gut microbiota are associated with the presence of a FAO phenotype and lower specific IgE response to mites and Ascaris.
Disease of the peripheral (or small) airways is fundamental in asthma, being closely related to symptoms (or lack of control of them), airway hyperresponsiveness, spirometric abnormalities, risk of loss of control, or exacerbations and inflammation. Current technology now allows routine measurement of peripheral airway function. Having a working concept of peripheral airways disease in asthma is arguably very useful to clinicians and beneficial to patients because it allows a more comprehensive assessment of asthma severity (rather than just symptoms alone, which is the norm), tracking of progress or deterioration, and assessing response to treatment. Oscillometry is a sensitive way to monitor the peripheral airways, whereas multiple breath nitrogen washout parameters are excellent measures of future risk. In the longer term, physiologic measurements will be crucial in research to define causes and find new disease-modifying treatments.
Purpose:
The purpose of this study was to determine how four different definitions of bronchodilator response (BDR) relate to asthma control and asthma symptom burden in a large population of participants with poorly controlled asthma.
Procedures:
We examined the baseline change in FEV1 and FVC in response to albuterol among 931 participants with poorly controlled asthma pooled from three clinical trials conducted by the American Lung Association - Airways Clinical Research Centers. We defined BDR based on four definitions and analyzed the association of each with asthma control as measured by the Asthma Control Test or Asthma Control Questionnaire, and asthma symptom burden as measured by the Asthma Symptom Utility Index.
Main findings:
A BDR was seen in 31-42% of all participants, depending on the definition used. There was good agreement among responses (kappa coefficient 0.73 to 0.87), but only 56% of participants met all four definitions for BDR. A BDR was more common in men than women, in Blacks compared to Whites, in non-smokers compared to smokers, and in non-obese compared to obese participants. Among those with poorly controlled asthma, 35% had a BDR compared to 25% of those with well controlled asthma, and among those with a high symptom burden, 34% had a BDR compared to 28% of those with a low symptom burden. After adjusting for age, sex, height, race, obesity and baseline lung function, none of the four definitions was associated with asthma control or symptom burden.
Conclusion:
A BDR is not associated with asthma control or symptoms in people with poorly controlled asthma, regardless of the definition of BDR used. These findings question the clinical utility of a BDR in assessing asthma control and symptoms.
INTRODUCTION: Variable expiratory airow due to bronchoconstriction, airway wall thickening and increased mucus is an obvious feature in asthma. Variable airow obstruction is evidenced by reversibility of FEV1 following a bronchodilator inhalation. PFT (Pulmonary Function Testing) using spirometry is often used for the estimation of FEV1. Reversibility is not uniform in all cases and vary with respect to severity and control of asthma. AIMS & OBJECTIVES: 1) To determine the control of asthma in 5-15-year-old children using GINA checklist and estimate FEV1 before and after SABA nebulisation. 2) To nd out the association between FEV1 reversibility and control of asthma. MATERIALS & METHODS: This cross-sectional study included 90 consecutive 5-15-year-old-children with a clinical diagnosis of asthma attending the Paediatric OPD of a teaching hospital from October-May 2021. The symptoms, signs, comorbidities, treatment, compliance and assessment of control of asthma into 2 subgroups: Well-controlled and Partly-controlled/Uncontrolled asthma, as per GINA 2020 were recorded. All were subjected to spirometry for assessment of FEV1 before and 20 minutes after nebulisation with SABA. Depending upon FEV1, they were grouped as those with >12% reversibility and <12% reversibility. Data analysed using SPSS 20.0, Paired t test for comparison of means, Chi-square test for statistical difference in proportion, and post hoc tests. The RESULTS: M:F ratio was 1.2:1, 52.2% were 10-15 years and 47.8% 5-10 years. 68.9% had partly/uncontrolled, the rest well-controlled asthma (38.1%). The difference between mean FEV1 before (67.9±10.6) and after nebulisation (80.6±9.7) was statistically signicant (p<0.00*). Among those with >12 reversibility, 64.5% were in partly/uncontrolled and 35.5% in well-controlled asthma and the difference was statistically signicant (p -0.013*). The CONCLUSION: nding in the study that 68.9% had partly/uncontrolled asthma is an eye-opener to optimise protocol-based treatment among children. The statistically signicant difference of >12% before and after nebulisation a marker of poor control was observed in 64.5% of partly/uncontrolled asthma compared to 35.5% of well controlled asthma. Hence, the persistence of a signicant degree of bronchodilator response noted in those with partly/uncontrolled asthma is recommended as an objective surrogate of poor asthma control in children who can co-operate for a PFT in order to optimise protocol-based treatment.
Asthma and chronic obstructive pulmonary disease (COPD) are both characterized by airway obstruction and share similar clinical manifestations. However, they differ in many respects related to underlying cause, mechanism of airway obstruction, pattern and progression of symptoms, and response to therapy. It remains unclear whether there is a unique physiologic phenotype that characterizes asthma-COPD overlap (ACO). This review describes the common and distinct physiologic tests that help define asthma and COPD and potentially how they may contribute to understanding the underlying physiology of ACO.
Background:
Given that airway obstruction in asthma is not always fully reversible, reduced bronchodilator reversibility (BDR) may be a special asthma phenotype.
Objective:
To explore the characteristics of BDRhigh/low phenotypes (defined using two BDR criteria) and their associations with asthma exacerbations (AEs).
Methods:
After baseline assessments, all patients were classified into BDRhigh or BDRlow phenotypes. This study consisted of 2 parts. Part I was a 12-month prospective observational cohort study designed to identify the clinical characteristics and associations with future AEs in BDRhigh/low phenotypes (n = 456). Part II, designed as a post hoc analysis of the data obtained in Part I, was conducted to assess the association between BDRhigh/low phenotypes and treatment responsiveness (n = 360).
Results:
Subjects with BDRlow phenotypes had better baseline asthma symptom control and was negatively associated with eosinophilic asthma and type 2 (T2) high asthma. During the 12-month follow-up, those with BDRlow phenotypes had a higher risk of severe AEs (SAEs) (guideline-based criterion: RRadj = 2.24, 95% CI = [1.25, 3.68]; Ward's criterion: RRadj = 2.46, 95% CI = [1.40, 4.00]) and moderate-to-severe AEs (MSAEs) (guideline-based criterion: RRadj = 1.83, 95% CI = [1.22, 2.56]; Ward's criterion: RRadj = 1.94, 95% CI = [1.32, 2.68]) in the following year according to logistic regression models. Similar findings were obtained with negative binominal regression models. BDRlow phenotype was a risk factor for an insensitive response to anti-asthma treatment (guideline-based criterion: ORadj = 1.96, 95% CI = [1.05, 3.65]; Ward's criterion: ORadj = 2.01, 95% CI = [1.12, 3.58]).
Conclusion:
We identified that BDRlow phenotype was associated with non-T2 high asthma and future AEs. These findings have clinically relevant implications for asthma management.
Background: The clinical implication of bronchodilator response (BDR) is not fully understood. However, BDR is frequently present in patients with chronic obstructive pulmonary disease (COPD). We identified the differences in clinical features regarding BDR. In addition, we divided BDR into BDR for forced expiratory volume in 1 s (FEV1) and BDR for forced vital capacity (FVC; i.e., BDR-FEV1 and BDR-FVC, respectively) and analyzed clinical significance.
Methods: We used data from the Korea COPD Subgroup Study, a multicenter cohort study of COPD patients recruited from 54 centers in South Korea since April 2012. We analyzed differences in baseline characteristics, 1-year exacerbation rate, and 3-year FEV1 decline between BDR negative and positive patients. Moreover, we analyzed the differences in clinical features between BDR-FEV1 positive and negative patients and between BDR-FVC positive and negative patients.
Results: Of the 2,181 patients enrolled in this study, 366 (16.8%) were BDR positive. BDR positive patients were more likely to be ever-smokers and to have a lower body mass index and higher symptom scores compared to BDR negative patients. Baseline FEV1 and FEV1/FVC were lower in the BDR positive compared to the BDR negative group (1.7 ± 0.6 and 1.6 ± 0.5, respectively, p < 0.01; 50.9 ± 12.1 and 46.5 ± 14.8, respectively, p < 0.01). BDR positive patients were more likely to have been diagnosed with asthma–COPD overlap and to receive inhaled corticosteroids (ICS) than BDR negative patients. Analyses of BDR-FEV1 and BDR-FVC patients showed that BDR-FVC patients had similar results to BDR patients with regard to smoking history, symptom scores, and lung function. BDR had no significant effect on 1-year moderate to severe or severe exacerbation rates or 3-year annual FEV1 decline. Interactive effects of ICS and BDR on the exacerbation rate were not significant in any group.
Conclusions: In this study, BDR positive patients were more likely to be ever-smokers and to have worse symptoms and lung function than BDR negative patients. BDR-FVC was associated with worse symptom control and lung function compared to BDR-FEV1. However, there were no significant differences in exacerbation rate or decline in lung function in any BDR group. In addition, the effects of ICS on exacerbations were not significant in any group.
Background
There are limited published data on the burden of moderate/severe uncontrolled asthma.
Methods
We conducted a systematic literature review to better understand the impact of moderate-to-severe asthma in the US, the UK, Germany, France, Italy, Spain, Canada, Japan, and Australia in terms of prevalence, clinical measures, health-related quality of life (HRQoL) and economic burden, for patients whose asthma is uncontrolled despite inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) therapy.
Results
The prevalence of uncontrolled asthma among patients with moderate/severe disease varied but was as high as 100% in some subgroups. Patients with uncontrolled asthma generally had poor lung function (mean/median pre-bronchodilator forced expiratory volume in 1 second [FEV1]: 1.69–2.45 L; mean/median pre-bronchodilator percent predicted FEV1: 57.2–79.7). There was also a substantial but variable exacerbation burden associated with uncontrolled asthma, with the annualised rate of exacerbations ranging from 1.30 to 7.30 when considering various patient subgroups. Furthermore, the annualised rate of severe exacerbations ranged from 1.66 to 3.60. The HRQoL burden measured using disease-specific and generic instruments consistently demonstrated substantial impairment of HRQoL for those with uncontrolled asthma; Asthma Quality of Life Questionnaire scores ranged from 3.00 to 5.20, whilst EurQol-5 Dimensions index scores ranged from 0.53 to 0.59. Direct, indirect and total costs together with consumption of other healthcare resources associated with managing uncontrolled asthma were also substantial in the population studied; no caregiver burden was identified.
Conclusions
Our findings suggest that significant unmet needs exist for patients with uncontrolled asthma despite the availability of ICS/LABA therapy. Novel treatments are needed to help reduce the burden to patients, healthcare systems and society.
Objective
This study analyzed whether the persistence of both reversible airway obstruction (RAO) and elevated BE counts was associated to reduced asthma control and accelerated lung function decline in treated severe asthmatics.
Methods
202 severe asthmatics were studied after 12‐120 months of step‐5 treatment associated to anti‐IgE therapy. Following treatments, reversibility tests, after inhaling 400 mcg of Salbutamol, were performed. FEV1>12% or ≤12% changes differentiated RAO+ from RAO‐ subjects. Blood eosinophil (BE) counts after treatment were considered.
Results
Pre‐/post‐treatment bronchodilator FEV1% and ACT were lower (61%[50‐71], 74.4%[62.5‐83.7] and 20[18‐22]), whereas BE were higher (380 cells/µL [170‐590]) in RAO+ compared to RAO‐ subjects (77%[64‐88], p=0.0001, 81.8%[66.1‐94.3], p=0.0001, 21[18‐23], p=0.045 and 230 cells/µL [80‐360], p=0.003). A negative relationship between SABA‐induced FEV1% changes and pre‐bronchodilator FEV1% (β= ‐0.551%;p=0.0001) and ACT (β= ‐0.059;p=0.038) was found. Conversely, post‐treatment BE levels were positively related (β=145.565 cells/µL;p=0.003) to FEV1>12% increases. A rising trend of pre‐/post‐bronchodilator FEV1% in time was observed in RAO‐ subjects with BE<300 cells/µL. Conversely, we highlighted significant declining tendencies of pre/post‐bronchodilator FEV1% in RAO+ patients with BE>300 cells/µL reaching lower values after more than 36 months of step‐5 treatment (59.6%[39.9‐72.1] vs 74[66.5‐89.2] of RAO+ individuals with BE<300 cells/µL [p=0.026] and 81.6%[66.1‐91.8] of RAO‐subjects with BE>300 cells/µL [p=0.009]).
Conclusion
Persistent SABA‐induced FEV1>12%, especially when associated to BE>300 cells/mL, may be a marker of accelerated lung function decline in severe asthmatics despite maximal step‐5 treatment. The highest bronchodilation associated to the lowest BE levels should be the main goal of asthma treatment to prevent such decline.
Objective:
To evaluate the impact of pediatric asthma on patients of a specialized outpatient clinic in Southern Brazil.
Methods:
The study included children aged 8 to 17 years old with asthma diagnosis (mild, moderate and severe) under treatment at the asthma clinic of Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Brazil. Measurements of spirometry, quality of life, disease control and atopy tests were applied.
Results:
A total of 66 children were included in the study and divided into groups, according to the severity of the disease: mild, moderate or severe asthma. The results showed similarities in both the treatment and the impact of asthma between groups, except for adherence to treatment: the group with mild asthma showed least adherence to treatment, and the group with severe asthma, greater adherence (p=0.011). As to school absenteeism, the group with severe asthma showed higher frequency (p=0.012), with over 10 days per year (p=0.043). Spirometry showed lower volume/capacity for the group with moderate asthma, followed by the groups with severe and mild asthma. All groups had a high prevalence of allergic asthma, with mites as the main allergens. For quality of life (QOL), and health-related quality of life (HRQOL) levels, there were no differences between groups. In addition, the values were close to the acceptable levels for the total score and for each one of the six domains. The same occurred for the HRQOL-asthma module.
Conclusions:
QOL and HRQOL present acceptable levels regardless of the severity of the disease.
Introduction and objectives:
Functional and inflammatory measures have been recommended to corroborate asthma diagnosis in schoolchildren, but the evidence in this regard is conflicting. We aimed to determine, in real-life clinical situation, the value of spirometry, spirometric bronchial reversibility to salbutamol (BDR), bronchial responsiveness to methacholine (MCT) and fractional exhaled nitric oxide (FENO), to corroborate the diagnosis of asthma in children on regular inhaled corticosteroids (ICS) referred from primary care.
Methods:
One hundred and seventy-seven schoolchildren with mild-moderate persistent asthma, on treatment with regular ICS, participated in the study. Abnormal tests were defined as FENO ≥ 27 ppb, BDR (FEV1 ≥ 12%) and methacholine PC20 ≤ 4 mg/mL.
Results:
The proportions of positive BDR, FENO and MCT, were 16.4%, 33.3%, and 87.0%, respectively. MCT was associated with FENO (p < 0.03) and BDR (p = 0.001); FENO was associated with BDR (p = 0.045), family history of asthma (p = 0.003) and use of asthma medication in the first two years of life (p = 0.004). BDR was significantly related with passive tobacco exposure (p = 0.003).
Conclusions:
Spirometry, BDR and BDR had a poor performance for corroborating diagnosis in our asthmatic children on ICS treatment; on the contrary, MCT was positive in most of them, which agrees with previous reports. Although asthma tests are useful to corroborate asthma when positive, clinical diagnosis remains the best current approach for asthma diagnosis, at least while better objective and feasible measurements at the daily practice are available. At present, these tests may have a better role for assessing the management and progression of the condition.
Background:
Persistent bronchodilator response (BDR) following diagnosis of asthma is an under-recognized treatable trait, associated with worse lung function and asthma control. The forced oscillation technique (FOT) measures respiratory system impedance and BDR cutoffs have been proposed for healthy adults, however relevance in asthma is unknown. We compared BDR cutoffs using FOT and spirometry in asthma and the relationship with asthma control.
Methods:
Data from patients with asthma who withheld bronchodilator medication for at least eight hours prior to a tertiary Airways clinic visit was reviewed. All subjects performed FOT and spirometry before and after salbutamol, and completed an asthma control test. FOT parameters examined included respiratory system resistance (R5) and reactance (X5) at 5Hz, and area under the reactance curve (AX). BDR was defined by standard recommendations for spirometry and based on the 95th percentile of BDR in healthy adults for FOT.
Results:
52 subjects (18 male; mean age 53±18 years) were included. BDR was identified more frequently by FOT than spirometry (54% vs 27% subjects). BDR assessed by X5 and AX, but not R5, were associated with spirometric BDR (χ2 p<0.01) and correlated with asthma control (X5: rs=-0.36, p<0.01; AX: rs=0.34, p=0.01). BDR measured by reactance parameters identified more subjects with poor asthma control than spirometry (AX 69% vs spirometry 41%).
Conclusion:
BDR assessed using FOT can identify poor asthma control. Reactance parameters were more sensitive in identifying poor asthma control than spirometry, supporting the use of FOT to complement spirometry in the clinical management of asthma.
Background:
Our objective was to determine those characteristics associated with reversibility of airflow obstruction and response to maximal bronchodilation in children with severe asthma through the Severe Asthma Research Program (SARP).
Methods:
We performed a cross-sectional analysis evaluating children ages 6 to 17 years with nonsevere asthma (NSA) and severe asthma (SA). Participants underwent spirometry before and after 180 µg of albuterol to determine reversibility (≥12% increase in FEV1 ). Participants were then given escalating doses up to 720 µg of albuterol to determine their maximum reversibility.
Results:
We evaluated 230 children (n = 129 SA, n = 101 NSA) from five centers across the United States in the SARP I and II cohorts. SA (odds ratio [OR], 2.08, 95% confidence interval [CI], 1.05-4.13), second-hand smoke exposure (OR, 2.81, 95%CI, 1.23-6.43), and fractional exhaled nitric oxide (FeNO; OR, 1.97, 95%CI, 1.35-2.87) were associated with increased odds of airway reversibility after maximal bronchodilation, while higher prebronchodilator (BD) FEV1 % predicted (OR, 0.91, 95%CI, 0.88-0.94) was associated with decreased odds. In an analysis using the SARP III cohort (n = 186), blood neutrophils, immunoglobulin E (IgE), and FEV1 % predicted were significantly associated with BD reversibility. In addition, children with BD response have greater healthcare utilization. BD reversibility was associated with reduced lung function at enrollment and 1-year follow-up though less decline in lung function over 1 year compared to those without reversibility.
Conclusions:
Lung function, that is FEV1 % predicted, is a predictor of BD response in children with asthma. Additionally, smoke exposure, higher FeNO or IgE level, and low peripheral blood neutrophils are associated with a greater likelihood of BD reversibility. BD response can identify a phenotype of pediatric asthma associated with low lung function and poor asthma control.
Theoretical non-linear modeling of exhaled nitric oxide has revealed extended flow-independent parameters that could explain where or how nitric oxide is produced in the lung and transferred to the airway gas stream. We aimed to evaluate the associations of bronchial hyperresponsiveness and bronchodilator response with extended flow-independent nitric oxide parameters.
Nitric oxide (30, 50, 100, 200 mL/s) was measured in 432 children with asthma on the same day as either methacholine challenge test (n=156) or spirometry with bronchodilator (n=276; 96 previously diagnosed with asthma and treated with inhaled corticosteroid, 37 with acute exacerbation treated with systemic corticosteroid). We additionally included 107 healthy controls for evaluation of the suitability of the non-linear model of exhaled nitric oxide.
In asthmatic children, response dose ratio of methacholine challenge test was correlated positively with bronchial nitric oxide (JawNO) and airway tissue nitric oxide (CawNO) (r= 0.367 and r = 0.299, respectively; both p<0.001), while the change in forced expiratory volume in 1 s, representing bronchodilator response, was associated positively with only JawNO (r=0. 216, p<0.001). On multiple regression, JawNO, CawNO, and diffusing capacity of NO (DawNO) were significantly associated with response dose ratio. JawNO was significantly associated with change in forced expiratory volume in children with stable asthma but not those with acute exacerbation.
Our findings suggest that bronchial hyperresponsiveness is associated with CawNO while factors other than airway tissue inflammation could affect bronchodilator response in children with mild asthma. Systemic corticosteroid use during asthma exacerbation could affect the association of bronchodilator response with extended nitric oxide parameters.
Fraction of exhaled nitrous oxide (FeNO) is a known marker of airway inflammation and a topic of recent investigation for asthma control in children.
OBJECTIVE: To investigate the relationship among FeNO and bronchodilator response measured by spirometry and types of inhaled corticosteroids (ICS).
METHODS: A one-year review of children tested with spirometry and FeNO in a regional pediatric asthma centre was conducted.
RESULTS: A total of 183 children were included (mean [± SD] age 12.8±2.8 years). Fluticasone was used most commonly (n=66 [36.1%]), followed by ciclesonide (n=50 [27.3%]). Most children (n=73 [39.9%]) had moderate persistent asthma. Increased FeNO was associated with percent change in forced expiratory volume in 1 s (FEV
1
) after bronchodilator adjusted for allergic rhinitis, parental smoking and ICS type (B=0.08 [95% CI 0.04 to 0.12]; P
Outcomes of pulmonary physiology have a central place in asthma clinical research.
At the request of National Institutes of Health (NIH) institutes and other federal agencies, an expert group was convened to provide recommendations on the use of pulmonary function measures as asthma outcomes that should be assessed in a standardized fashion in future asthma clinical trials and studies to allow for cross-study comparisons.
Our subcommittee conducted a comprehensive search of PubMed to identify studies that focused on the validation of various airway response tests used in asthma clinical research. The subcommittee classified the instruments as core (to be required in future studies), supplemental (to be used according to study aims and in a standardized fashion), or emerging (requiring validation and standardization). This work was discussed at an NIH-organized workshop in March 2010 and finalized in September 2011.
A list of pulmonary physiology outcomes that applies to both adults and children older than 6 years was created. These outcomes were then categorized into core, supplemental, and emerging. Spirometric outcomes (FEV(1), forced vital capacity, and FEV(1)/forced vital capacity ratio) are proposed as core outcomes for study population characterization, for observational studies, and for prospective clinical trials. Bronchodilator reversibility and prebronchodilator and postbronchodilator FEV(1) also are core outcomes for study population characterization and observational studies.
The subcommittee considers pulmonary physiology outcomes of central importance in asthma and proposes spirometric outcomes as core outcomes for all future NIH-initiated asthma clinical research.
Asthma Control Test (ACT) is a simple tool for assessing the level of asthma control in clinical practice, and it has been validated in comparison with a general clinical assessment of asthma control, including forced expiratory volume in the first second (FEV(1)).
To evaluate the relationship between ACT score and clinical and functional findings of asthma control and biomarkers of airway inflammation.
A total of 68 asthmatic patients observed in our asthma clinic (33 regularly treated with inhaled corticosteroids (ICS) and 35 ICS-naïve) filled ACT questionnaire and underwent the following measurements: (a) FEV(1) before and after salbutamol; (b) exhaled nitric oxide; (c) bronchial hyperresponsiveness to methacholine; (d) sputum eosinophil count; and (e) daytime and nighttime symptoms, rescue salbutamol, and twice-daily peak expiratory flow (PEF) recording on a 4-week diary card.
ACT score significantly correlated with symptom score, rescue medication use, and PEF variability, but not with FEV(1), FEV(1) reversibility, and markers of airway inflammation, which could not distinguish controlled from uncontrolled patients according to ACT, regardless of ICS treatment.
ACT score is a valid tool to simply assess the current level of asthma control in terms of symptoms, rescue medication use, and PEF variability. Pulmonary function and biomarkers of airway inflammation are not related to the clinical asthma control as assessed by ACT and may represent additional measurements potentially useful in asthma management.
Differences in COPD classification have been shown in population data sets when using fifth percentiles as the lower limit of normal (LLN) vs the current GOLD (Global Initiative for Chronic Obstructive Lung Disease) guidelines of FEV(1)/FVC < 0.70 for detecting airway obstruction and an FEV(1) of 80% predicted for detecting and classifying the severity of COPD (GOLD/PP). Many lung function laboratories use 80% predicted to determine whether results are abnormal. Misclassification of the full range of lung diseases in large patient groups when using GOLD/PP criteria instead of the LLN has not been explored previously.
We determined the discrepancy rates in pulmonary function test interpretation between the GOLD/PP and LLN methods on prebronchodilator lung function results from a large number of adult patients from the United Kingdom, New Zealand, and the United States.
In 11,413 patients, the GOLD/PP method misclassified 24%. Ten percent of patients who had normal lung function were falsely classified with a disease category, and 7% of patients were falsely attributed with emphysema. The GOLD/PP method gave false-positive classifications for airflow obstruction and restrictive defects to significantly more men (P < .01) and older patients (P < .0001) and also missed airflow obstruction and restrictive defects in younger patients (P < .0001).
Using lung function tests on their own with 80% predicted and fixed cut points to determine whether a test is abnormal could misdiagnose > 20% of patients referred for pulmonary function tests. The GOLD/PP method introduces clinically important biases in assessing disease status that could affect allocation to treatment groups. This misclassification is avoided by using the LLN based on the fifth-percentile values.
The Severe Asthma Research Program cohort includes subjects with persistent asthma who have undergone detailed phenotypic characterization. Previous univariate methods compared features of mild, moderate, and severe asthma.
To identify novel asthma phenotypes using an unsupervised hierarchical cluster analysis.
Reduction of the initial 628 variables to 34 core variables was achieved by elimination of redundant data and transformation of categorical variables into ranked ordinal composite variables. Cluster analysis was performed on 726 subjects.
Five groups were identified. Subjects in Cluster 1 (n = 110) have early onset atopic asthma with normal lung function treated with two or fewer controller medications (82%) and minimal health care utilization. Cluster 2 (n = 321) consists of subjects with early-onset atopic asthma and preserved lung function but increased medication requirements (29% on three or more medications) and health care utilization. Cluster 3 (n = 59) is a unique group of mostly older obese women with late-onset nonatopic asthma, moderate reductions in FEV(1), and frequent oral corticosteroid use to manage exacerbations. Subjects in Clusters 4 (n = 120) and 5 (n = 116) have severe airflow obstruction with bronchodilator responsiveness but differ in to their ability to attain normal lung function, age of asthma onset, atopic status, and use of oral corticosteroids.
Five distinct clinical phenotypes of asthma have been identified using unsupervised hierarchical cluster analysis. All clusters contain subjects who meet the American Thoracic Society definition of severe asthma, which supports clinical heterogeneity in asthma and the need for new approaches for the classification of disease severity in asthma.
The assessment of asthma control is pivotal to the evaluation of treatment response in individuals and in clinical trials. Previously, asthma control, severity, and exacerbations were defined and assessed in many different ways.
The Task Force was established to provide recommendations about standardization of outcomes relating to asthma control, severity, and exacerbations in clinical trials and clinical practice, for adults and children aged 6 years or older.
A narrative literature review was conducted to evaluate the measurement properties and strengths/weaknesses of outcome measures relevant to asthma control and exacerbations. The review focused on diary variables, physiologic measurements, composite scores, biomarkers, quality of life questionnaires, and indirect measures.
The Task Force developed new definitions for asthma control, severity, and exacerbations, based on current treatment principles and clinical and research relevance. In view of current knowledge about the multiple domains of asthma and asthma control, no single outcome measure can adequately assess asthma control. Its assessment in clinical trials and in clinical practice should include components relevant to both of the goals of asthma treatment, namely achievement of best possible clinical control and reduction of future risk of adverse outcomes. Recommendations are provided for the assessment of asthma control in clinical trials and clinical practice, both at baseline and in the assessment of treatment response.
The Task Force recommendations provide a basis for a multicomponent assessment of asthma by clinicians, researchers, and other relevant groups in the design, conduct, and evaluation of clinical trials, and in clinical practice.
The importance of reversible airflow obstruction to the prognosis of asthma and chronic obstructive pulmonary disease (COPD) is not clear. We tested the hypothesis that reversibility to corticosteroid and bronchodilator is not an independent predictor of prognosis, but merely reflects a component of the maximal attainable lung function, which is the best spirometric predictor of survival. During a 6-yr period (1983-1988), 1,586 subjects with asthma or COPD underwent standardized bronchodilator and corticosteroid reversibility tests at a chest clinic in Copenhagen. The vital status was obtained by September 1997. The relationship between mortality and age, gender, smoking, FEV1, and reversibilities was examined by Cox proportional hazards analyses. Of 1,586 subjects, 850 had died before September 1997. Age, smoking, and FEV1 were significant predictors of mortality. After controlling for baseline FEV1, bronchodilator and corticosteroid reversibility were significantly associated with better survival. However, after controlling for best FEV1 all reversibilities became nonsignificant and nonpredictive. The combined use of corticosteroid and bronchodilator reversibility in survival analyses is a novel approach, and we have shown that both contribute to survival prediction to the extent that they modify FEV1. However, reversibility per se does not influence survival in subjects with moderate to severe asthma or COPD.
Written asthma action plans based on personal best peak expiratory flow (PEF) consistently improve health outcomes, whereas those based on predicted PEF do not. Guidelines state that personal best PEF should be assessed over 2-3 weeks during good asthma control, but it is unclear how long to wait after commencing or changing treatment.
Electronically recorded spirometric data from 61 subjects with initially poorly controlled asthma from a 72 week budesonide study were analysed. For each week, average morning pre-bronchodilator PEF was calculated and personal best PEF was determined as the highest PEF in the previous 2 weeks. The time to plateau was defined as the week beyond which no further improvement occurred.
At baseline, average morning PEF was 61% predicted and personal best PEF was 87% predicted. Personal best PEF from twice daily monitoring increased to a plateau of 95% predicted (p<0.0001) after only 3 weeks of budesonide treatment. However, average morning PEF continued to improve for 3 months and "as needed" reliever use for 7 months.
Personal best PEF is a useful concept for asthma self-management plans when determined as the highest PEF over the previous 2 weeks. With twice daily monitoring, personal best PEF reaches plateau levels after only a few weeks of corticosteroid treatment.
High bronchodilator reversibility (HR) in adult asthma is associated with distinct clinical characteristics. This analysis compares lung function, biomarker profiles and disease control in HR and low reversibility (LR) asthma patients.
A retrospective analysis was performed with data from 2 completed clinical trials of similar design (NCT01018550 and NCT01199289). Patients were divided into HR and LR subgroups based on their response to bronchodilators (HR = ΔFEV1 post-bronchodilator ≥ +20%). Serum IgE, blood eosinophils, and exhaled nitric oxide (FeNO), biomarkers commonly used to stratify patients into Th2-high vs. Th2-low phenotypes, were measured in "not well controlled" (1.5 ≤ ACQ ≤ 2.143) and "very poorly controlled" (ACQ > 2.143) patients.
The majority of patients in HR and LR subgroups displayed Th2-low biomarker profiles and very poor disease control. HR was more frequently associated with Th2-high biomarkers (40.1% vs. 29.4%; p=0.006), lower lung function (FEV1: 63.5±7.7% vs. 67.9±8.4% pred; p<0.001), and atopy (93.7% vs. 86.5%; p=0.005).
HR is a physiological indicator of reduced lung function, and is more often associated with elevations in Th2 biomarkers than LR in moderate-to-severe asthma. However, the majority of HR and LR patients in this analysis displayed a Th2-low biomarker profile. Moreover, a Th2-high biomarker profile was not associated with worse disease control.
The way in which spirometry is interpreted can lead to misdiagnosis of chronic obstructive pulmonary disease (COPD) resulting in inappropriate treatment. We compared the clinical relevance of 2 criteria for defining a low ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC): the fixed ratio and the lower limit of normal.
We analyzed data from the cross-sectional phase of the population-based Canadian Cohort of Obstructive Lung Disease (CanCOLD) study. We determined associations of the spirometric criteria for airflow limitation with patient-reported adverse outcomes, including respiratory symptoms, disability, health status, exacerbations, and cardiovascular disease. Sensitivity analyses were used to explore the impact of age and severity of airflow limitation on these associations.
We analyzed data from 4,882 patients aged 40 years and older. The prevalence of airflow limitation was 17% by fixed ratio and 11% by lower limit of normal. Patients classified as having airflow limitation by fixed ratio only had generally small, nonsignificant increases in the odds of adverse outcomes. Patients having airflow limitation based on both fixed ratio and lower limit of normal had larger, significant increases in odds. But strongest associations were seen for patients who had airflow limitation by both fixed ratio and lower limit of normal and also had a low FEV1, defined as one less than 80% of the predicted value.
Our results suggest that use of the fixed ratio alone may lead to misdiagnosis of COPD. A diagnosis established by both a low FEV1/FVC (according to fixed ratio and/or lower limit of normal) and a low FEV1 is strongly associated with clinical outcomes. Guidelines should be reconsidered to require both spirometry abnormalities so as to reduce overdiagnosis of COPD.
© 2015 Annals of Family Medicine, Inc.
Introduction
Although corticosteroid therapy for asthma improves lung function and reduces airway inflammation, the relation between these two events is unclear. This article investigates associations between changes in bronchial inflammation and lung function during high-dose inhaled corticosteroid therapy for asthma.
Methods
Nine subjects with atopic asthma received high-dose inhaled fluticasone propionate (FP), 2,000 μg/d for 8 weeks. Fiberoptic bronchoscopy with endobronchial biopsies, spirometry, and histamine provocation challenge were performed on each subject at baseline, after 2 weeks, and again after 8 weeks of therapy. Spearman rank correlation coefficients between changes in parameters of bronchial inflammation and lung function were computed.
Results
As expected, significant down-regulation of airway inflammation and improvements in lung function were observed after both short-term and long-term therapy with high-dose inhaled FP. During corticosteroid therapy, changes in lymphocyte and macrophage numbers in bronchial biopsy specimens were closely correlated. Changes in EG1+ eosinophils were associated with changes in EG2+ eosinophils after 8 weeks of therapy. Although changes in airway inflammation and changes in lung function were not closely associated after 2 weeks of therapy, changes in eosinophils (EG1) in bronchial biopsy specimens correlated with changes in bronchodilator response (r = 0.77, p = 0.016) after 8 weeks of therapy.
Conclusion
In patients with atopic asthma, changes in bronchial eosinophils and lung function during steroid therapy are closely related but do not occur simultaneously.
IntroductionThe current goal of asthma treatment is to achieve and maintain control. This study aimed to explore the relationship between the ACT (Asthma Control Test) questionnaire and the levels of control according to GINA (Global Initiative for Asthma) to establish the cut-off points for the ACT and evaluate its relationship with lung function and fractionated exhaled nitric oxide level (FeNO).
Background
Data from long-term follow-up studies of patients with well-characterized asthma are limited. We studied all-cause and cause-specific mortality and risk factors in a large cohort of adults with asthma.
Methods
A total of 1,075 adult patients with asthma were recruited consecutively from an outpatient clinic from 1974 to 1990 and followed up until the end of 2011. Subjects were classified as having allergic or nonallergic asthma on the basis of a detailed history, spirometric tests, tests for IgE-mediated allergy (skin prick tests and radioallergosorbent test), and bronchial challenge tests. Information on vital status and cause of death were obtained from the Danish Death Register and the Danish National Board of Health. All-cause mortality was also studied in an age- and sex-matched group of subjects without asthma.
Results
All-cause mortality was increased significantly among patients with asthma compared with control subjects (261 cases vs 124 control subjects; relative risk (RR), 2.1; 95% CI, 1.4-3.0; P < .001). The excess mortality was primarily due to death from obstructive lung disease (95 deaths). Subsequent death from asthma was significantly associated with age (P < .001), level of FEV1 % predicted (P < .001), bronchodilator reversibility (P < .01), peripheral eosinophil count (P < .0001), and previous acute hospital contacts for asthma (P = .002) at enrollment. No significant association was found between smoking habits or self-reported symptom severity, and subsequent death from asthma. After adjusting for age and level of FEV1 % predicted, nonallergic asthma was associated with a higher risk of death from asthma (RR, 1.9; 95% CI, 1.1-3.2; P = .001).
Conclusion
This 25-year prospective study of a large cohort of adults with well-characterized asthma showed an excess mortality compared with matched control subjects, to a large extent explained by death from obstructive lung disease.
Bronchodilator response (BDR) is assessed to estimate the reversibility of airflow obstruction. Bronchial hyperresponsiveness (BHR) is a characteristic feature of asthma and is usually measured by means of bronchial challenges using direct or indirect stimuli. The aim of the present study was to compare BHR to methacholine (direct) and that to adenosine 5’-monophosphate (AMP) (indirect) with regard to their relationships to BDR in asthmatic children.
Methacholine and AMP challenge tests were performed on 138 children with mild-to-moderate asthma, and the provocative concentration causing a 20% decline in forced expiratory volume in 1 s (FEV 1 ) (PC 20 ) was determined for each challenge. BDR was calculated as the change in FEV 1 , expressed as a percentage of the initial value, after inhalation of 400 μg salbutamol.
Methacholine PC 20 correlated significantly but weakly with BDR (r = -0.254; p = 0.003). However, there was a significant and strong correlation between AMP PC 20 and BDR (r = -0.489; p = 0.000). For AMP PC 20 , the relationship was closer than for methacholine PC 20 (p = 0.024 for comparison between correlation coefficients). The same figures were observed when BDR was expressed as a percentage of the predicted value.
A stronger correlation of BDR with AMP PC 20 than with methacholine PC 20 suggests that BDR may be better reflected by BHR as assessed by AMP challenge than by methacholine challenge.
The current goal of asthma treatment is to achieve and maintain control. This study aimed to explore the relationship between the ACT (Asthma Control Test) questionnaire and the levels of control according to GINA (Global Initiative for Asthma) to establish the cut-off points for the ACT and evaluate its relationship with lung function and fractionated exhaled nitric oxide level (FeNO).
A multi-centre prospective study including 441 patients followed up in an outpatient Chest Clinic. A clinical protocol was followed, and FeNO, spirometry and ACT performed. Disease was classified according to levels of control using GINA. The study analysed sensitivity, specificity and area under the curve (ROC), and the ACT cut-off points. We studied the differences between the functional parameters and FeNO between levels of control.
For controlled asthma the cut-off obtained was ACT> or =21 (area under the curve 0.791) and for uncontrolled < or =18 (AUC 0.774). We found significant differences in FeNO levels and pulmonary function among ACT> or =21 and ACT< or =18, although only 26.3% of patients with ACT< or =18 had a FEV1 <80% and 40% higher FeNO (> or =35 ppb). We found a correlation between baseline FEV1 and ACT (r=0.19, P<0.01) and between ACT and FeNO (r=-0.16, P<0.01).
The cut-off points would be, for controlled asthma ACT> or =21, partly controlled asthma ACT=19-20 and uncontrolled asthma ACT< or =18. A more complete assessment would require including monitoring operating parameters and FeNO.
Bronchial hyperresponsiveness to 5-adenosine mono-phosphate (AMP) is a marker of airway inflammation. Inhaled corticosteroids and antileukotrienes are used as anti-inflammatory drugs for the treatment of asthma. To find out if these two drugs exert their protection in an additive fashion, we compared the effects of acute treatment with inhaled beclomethasone (BDP) and montelukast (ML), alone or in combination, on methacholine and AMP induced bronchoconstriction. 15 asthmatic patients undertook methacholine and AMP challenges at baseline and after receiving ML or BDP, alone or in combination, in a randomized, double-blind, double-dummy placebo-controlled, crossover design. BDP pretreatment significantly increased the AMP PC(20) value (68.34+/-15.9mg/mL) as compared to placebo (22.87+/-5.7mg/mL). Combined treatment, BDP plus ML, afforded a further significant increase of AMP PC(20) (154.57+/-55.0mg/mL) as compared to each single treatment. The significant protection exerted by combined treatment as compared to each single active treatment was also demonstrated by the change of AMP PC(20) doubling dose as compared to placebo and each single active treatment. Our findings suggest that these two agents exert their acute additive protection against AMP induced bronchoconstriction acting on distinct inflammatory pathways and their combined use might provide greater protection against inflammatory response elicited by AMP than either drug alone.
International guidelines on asthma management indicate that the primary goal of treatment should be optimum asthma control. The aim of this study was to develop and validate the Asthma Control Questionnaire (ACQ). The authors generated a list of all symptoms used to assess control and sent it to 100 asthma clinicians who were members of guidelines committees (18 countries). They scored each symptom for its importance in evaluating asthma control. From the 91 responses, the five highest scoring symptoms were selected for the ACQ. In addition, there is one question on beta2-agonist use and another on airway calibre (total questions=7). The ACQ was tested in a 9-week observational study of 50 adults with symptomatic asthma. The ACQ and other measures of asthma health status were assessed at baseline, 1, 5 and 9 weeks. In patients whose asthma was stable between clinic visits, reliability of the ACQ was high (intraclass correlation coefficient (ICC)=0.90). The questionnaire was very responsive to change in asthma control (p<0.0001). Cross-sectional and longitudinal validity were supported by correlations between the ACQ and other measures of asthma health status being close to a priori predictions. In conclusion, the Asthma Control Questionnaire has strong evaluative and discriminative properties and can be used with confidence to measure asthma control.
Although corticosteroid therapy for asthma improves lung function and reduces airway inflammation, the relation between these two events is unclear. This article investigates associations between changes in bronchial inflammation and lung function during high-dose inhaled corticosteroid therapy for asthma.
Nine subjects with atopic asthma received high-dose inhaled fluticasone propionate (FP), 2,000 microg/d for 8 weeks. Fiberoptic bronchoscopy with endobronchial biopsies, spirometry, and histamine provocation challenge were performed on each subject at baseline, after 2 weeks, and again after 8 weeks of therapy. Spearman rank correlation coefficients between changes in parameters of bronchial inflammation and lung function were computed.
As expected, significant down-regulation of airway inflammation and improvements in lung function were observed after both short-term and long-term therapy with high-dose inhaled FP. During corticosteroid therapy, changes in lymphocyte and macrophage numbers in bronchial biopsy specimens were closely correlated. Changes in EG1+ eosinophils were associated with changes in EG2+ eosinophils after 8 weeks of therapy. Although changes in airway inflammation and changes in lung function were not closely associated after 2 weeks of therapy, changes in eosinophils (EG1) in bronchial biopsy specimens correlated with changes in bronchodilator response (r = 0.77, p = 0.016) after 8 weeks of therapy.
In patients with atopic asthma, changes in bronchial eosinophils and lung function during steroid therapy are closely related but do not occur simultaneously.
Exhaled nitric oxide (FE(NO)) was evaluated in children with asthma after 4 to 6 years of treatment with budesonide, nedocromil, or albuterol as needed.
FE(NO), spirometry, total eosinophil count, and serum eosinophil cationic protein levels were obtained from 118 children at the Denver site of the Childhood Asthma Management Program upon completion of treatment and after a 2- to 4-month washout.
Budesonide-treated patients had significantly lower median (1st, 3rd quartile) FE(NO) (21.5 [13.2, 84.4] vs 62.5 [26.2, 115.0] ppb, P <.01) and eosinophil cationic protein levels (17.4 [10.1, 24.3] vs 24.0 [15.4, 33.9] mg/dL, P =.05) compared with placebo, whereas no differences were noted between nedocromil and placebo groups. After washout, FE(NO) levels were similar between the three treatments. FE(NO) levels significantly correlated with degree of bronchial hyperresponsiveness, bronchodilator reversibility, allergen skin prick tests, serum IgE, and total eosinophil count. FE(NO) levels were also higher in patients with nocturnal symptoms and in patients requiring beta-agonist use at least once weekly.
Budesonide therapy was more effective than nedocromil in reducing FE(NO). Unfortunately, the effects of long-term budesonide were not sustained after its discontinuation. FE(NO) may be a complementary tool to current practice guidelines in assessing asthma control and medication response.
Asthma guidelines indicate that the goal of treatment should be optimum asthma control. In a busy clinic practice with limited time and resources, there is need for a simple method for assessing asthma control with or without lung function testing.
The objective of this article was to describe the development of the Asthma Control Test (ACT), a patient-based tool for identifying patients with poorly controlled asthma.
A 22-item survey was administered to 471 patients with asthma in the offices of asthma specialists. The specialist's rating of asthma control after spirometry was also collected. Stepwise regression methods were used to select a subset of items that showed the greatest discriminant validity in relation to the specialist's rating of asthma control. Internal consistency reliability was computed, and discriminant validity tests were conducted for ACT scale scores. The performance of ACT was investigated by using logistic regression methods and receiver operating characteristic analyses.
Five items were selected from regression analyses. The internal consistency reliability of the 5-item ACT scale was 0.84. ACT scale scores discriminated between groups of patients differing in the specialist's rating of asthma control (F = 34.5, P <.00001), the need for change in patient's therapy (F = 40.3, P <.00001), and percent predicted FEV(1) (F = 4.3, P =.0052). As a screening tool, the overall agreement between ACT and the specialist's rating ranged from 71% to 78% depending on the cut points used, and the area under the receiver operating characteristic curve was 0.77.
Results reinforce the usefulness of a brief, easy to administer, patient-based index of asthma control.
Several studies have demonstrated a poor relationship between measures of asthma control and lung function in patients with asthma. We sought to examine this relationship in a cohort of difficult to control asthmatics attending a hospital outpatient clinic. FEV1 % and asthma control scores (ACSs) were measured at the first clinic visit and at a follow-up visit. A total of 59 patients took part in the study. At the initial visit, FEV1 % correlated with limitation of activity (p = 0.002), shortness of breath (p = 0.02), wheezing (p = 0.029), and ACS (p = 0.014). However, at follow-up, there was no correlation between FEV1 % and any measured index of asthma control. When patients with severe fixed airflow obstruction were excluded from the analysis (n = 16), FEV1 % at follow-up became significantly correlated with night waking (p = 0.02), wheezing (p = 0.05), and ACS (p = 0.036). The improvement in asthma control score at follow-up was significantly and strongly associated (r = 0.51 for total asthma control, p < 0.001) with the improvement in lung function in patients without severe fixed airflow obstruction. Lung function was not associated with any measure of asthma control in patients with severe fixed airflow obstruction. FEV1 % correlates well with asthma symptoms in difficult asthma patients with poor control but not when control improves. This loss of relationship is due to subjects with severe fixed airflow obstruction where good subjective control does not exclude the presence of significant obstruction. How severe fixed airflow obstruction should be prevented, delayed, or managed in asthma requires further research.
Epidemiologic evidence related to asthma control in patients from the general population is scanty.
We sought to assess asthma control in several European centers according to the Global Initiative for Asthma (GINA) guidelines and to investigate its determinants.
In the European Community Respiratory Health Survey II (1999-2002), 1241 adults with asthma were identified and classified into inhaled corticosteroid (ICS) users and non-ICS users in the last year. Control was assessed in both groups by using the GINA proposal (controlled, partly controlled, and uncontrolled asthma), and it was related to potential determinants.
Only 15% (95% CI, 12% to 19%) of subjects who had used ICSs in the last year and 45% (95% CI, 41% to 50%) of non-ICS users had their asthma under control; individuals with uncontrolled asthma accounted for 49% (95% CI, 44% to 53%) and 18% (95% CI, 15% to 21%), respectively. Among ICS users, the prevalence of uncontrolled asthma showed great variability across Europe, ranging from 20% (95% CI, 7% to 41%; Iceland) to 67% (95% CI, 35% to 90%; Italy). Overweight status, chronic cough and phlegm, and sensitization to Cladosporium species were associated with poor control in ICS users. About 65% and 87% of ICS users with uncontrolled and partly controlled asthma, respectively, were on a medication regimen that was less than recommended by the GINA guidelines.
Six of 7 European asthmatic adults using ICSs in the last year did not achieve good disease control. The large majority of subjects with poorly controlled asthma were using antiasthma drugs in a suboptimal way. A wide variability in asthma control emerged across Europe.
Greater attention should be paid to asthma management and to the implementation of the GINA guidelines.
Asthma is a serious health problem throughout the world. During the past two decades, many scientific advances have improved our understanding of asthma and ability to manage and control it effectively. However, recommendations for asthma care need to be adapted to local conditions, resources and services. Since it was formed in 1993, the Global Initiative for Asthma, a network of individuals, organisations and public health officials, has played a leading role in disseminating information about the care of patients with asthma based on a process of continuous review of published scientific investigations. A comprehensive workshop report entitled "A Global Strategy for Asthma Management and Prevention", first published in 1995, has been widely adopted, translated and reproduced, and forms the basis for many national guidelines. The 2006 report contains important new themes. First, it asserts that "it is reasonable to expect that in most patients with asthma, control of the disease can and should be achieved and maintained," and recommends a change in approach to asthma management, with asthma control, rather than asthma severity, being the focus of treatment decisions. The importance of the patient-care giver partnership and guided self-management, along with setting goals for treatment, are also emphasised.
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