Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Lung Sounds in Bronchial Asthma

Modern understanding of lung sounds started with a historical article by Forgacs. Since then, many studies have clarified the changes of lung sounds due to airway narrowing as well as the mechanism of genesis for these sounds. Studies using bronchoprovocation have shown that an increase of the frequency and/or intensity of lung sounds was a common finding of airway narrowing and correlated well with lung function. Bronchoprovocation studies have also disclosed that wheezing may not be as sensitive as changes in basic lung sounds in acute airway narrowing. A forced expiratory wheeze (FEW) may be an early sign of airway obstruction in patients with bronchial asthma. Studies of FEW showed that airway wall oscillation and vortex shedding in central airways are the most likely mechanisms of the generation of expiratory wheezes. Studies on the genesis of wheezes have disclosed that inspiratory and expiratory wheezes may have the same mechanism of generation as a flutter/flow limitation mechanism, either localized or generalized. In lung sound analysis, the narrower the airways are, the higher the frequency of breathing sounds is, and, if a patient has higher than normal breathing sounds, i.e., bronchial sounds, he or she may have airway narrowing or airway inflammation. It is sometimes difficult to detect subtle changes in lung sounds; therefore, we anticipate that automated analysis of lung sounds will be used to overcome these difficulties in the near future

Phenotype classification using the combination of lung sound analysis and fractional exhaled nitric oxide for evaluating asthma treatment

Background: We report the utility of combining lung sound analysis and fractional exhaled nitric oxide (FeNO) for phenotype classification of airway inflammation in patients with bronchial asthma.We investigated the usefulness of the combination of the expiration-to-inspiration sound power ratio in the mid-frequency range (E/I MF) of 200–400 Hz and FeNO for comprehensively classifying disease type and evaluating asthma treatment. Methods: A total of 233 patients with bronchial asthma were included. The cutoff values of FeNO and E/I MF were set to 38 ppb and 0.36, respectively, according to a previous study. The patients were divided into 4 subgroups based on the FeNO and E/I MF cutoff values. Respiratory function, the percentages of sputum eosinophils and neutrophils, and patient background characteristics were compared among groups. Results: Respiratory function was well controlled in the FeNO low/E/I MF low group (good control). Sputum neutrophil was higher and FEV1,%pred was lower in the FeNO low/E/I MF high group (poor control). History of childhood asthma and atopic asthma were associated with the FeNO high/E/I MF low group (insufficient control). The FeNO high/E/I MF high group corresponded to a longer disease duration, increased blood or sputum eosinophils, and lower FEV1/FVC (poor control). Conclusions: The combination of FeNO and E/I MF assessed by lung sound analysis allows the condition of airway narrowing and the degree of airway inflammation to be assessed in patients with asthma and is useful for evaluating bronchial asthma treatments. Keywords: Bronchial asthma, E/I MF, FeNO, Lung sound analysis, Phenotyp

A New Modality Using Breath Sound Analysis to Evaluate the Control Level of Asthma

Background: Reliable symptom assessment is essential in asthma management. We developed new technology for analyzing breath sounds and assessed its clinical usefulness for monitoring asthmatic children. Methods: Eighty asthmatic children and 59 non-asthmatic children underwent breath sound analysis in an asymptomatic state. Their asthma control was assessed by the Asthma Control TestTM or Childhood ACTTM scores and divided into two groups, namely, well-controlled (perfect) (n = 19) and not well-controlled (not perfect) (n = 61). Breath sounds were recorded using two sensors, located on the right anterior chest and trachea. We calculated the acoustic transfer characteristics between the two points, which indicated the relationship between frequencies and attenuation during breath sound propagation. Two indices of sound parameters, the chest wall sound index (CWI) and the tracheal sound index (TRI), were calculated from the transfer characteristics and tracheal sounds. We also developed a new parameter, the breath sound index (BSI), on a 2-dimensional diagram of CWI and TRI and tried to determine whether BSI may clarify asthma control better than CWI or TRI alone. Results: There was a significant difference in TRI and BSI between asthmatic and non-asthmatic children (p = 0.007, p < 0.001). There was a significant difference in CWI and TRI between the well-controlled and not-wellcontrolled groups (p < 0.001). BSI discriminated between the two groups accurately (p < 0.001). The sensitivity and specificity of BSI for asthma control were 83.6% and 84.2%, respectively. Conclusions: Asthma control could be evaluated using a new index calculated from breath sound analysis

Evaluation of airflow limitation using a new modality of lung sound analysis in asthmatic children

Background: Reliable assessment of not only symptoms but also lung function is essential in asthma management. We developed a new technology for analyzing lung sounds and assessed its clinical usefulness in asthmatic children. Methods: Forty-four children underwent lung sound recording with simultaneous airflow measurement using a sensor on the upper right anterior chest. We calculated a sound parameter index from the amplitude of inspiratory lung sounds at 700 Hz (ic700). ic700 were compared depending on flow and body size. In addition, 184 asthmatic children and 16 non-asthmatic children underwent lung sound analysis and lung function test in an asymptomatic state. In the asthma group, 135 children received treatment continually. The untreated asthma group included 28 children who had never received treatment continually and 21 children who had not been treated for at least 1 year. The asthmatic children were divided into four classes according to asthma severity. ic700 were compared depending on spirometric parameters and asthma severity classification. Results: The influences of flow and body size were negligible for ic700. ic700 correlated with FEV1%, MMF and FEF50 (r = −0.436, −0.339 and −0.302, respectively). There was a significant difference of ic700 between asthmatic and non-asthmatic children (p < 0.001), and ic700 correlated with the classification of asthma severity (p < 0.001). The ic700 scores of the severe group were higher than those of the intermittent group and non-asthmatic children. Conclusions: It was possible to evaluate airway dysfunction of asthma using ic700, which was calculated non-invasively by analyzing lung sounds alone, without measuring body size and airflow

Peripheral bronchial obstruction evaluation in patients with asthma by lung sound analysis and impulse oscillometry

Background: Computer-aided lung sound analysis (LSA) has been reported to be useful for evaluating airway inflammation and obstruction in asthma patients. We investigated the relation between LSA and impulse oscillometry with the evaluation of peripheral airway obstruction. Methods: A total of 49 inhaled corticosteroid-naive bronchial asthma patients underwent LSA, spirometry, impulse oscillometry, and airway hyperresponsiveness testing. The data were analyzed to assess correlations between the expiration: inspiration lung sound power ratio (dB) at low frequencies between 100 and 195 Hz (E/I LF) and various parameters. Results: E/I LF and X5 were identified as independent factors that affect V˙50,%predicted. E/I LF showed a positive correlation with R5 (r = 0.34, p = 0.017), R20 (r = 0.34, p = 0.018), reactance area (AX, r = 0.40, p = 0.005), and resonant frequency of reactance (Fres, r = 0.32, p = 0.024). A negative correlation was found between E/I LF and X5 (r = −0.47, p = 0.0006). E/I LF showed a negative correlation with FEV1/FVC(%), FEV1,%predicted, V˙50,%predicted, and V˙25,%predicted (r = −0.41, p = 0.003; r = −0.44, p = 0.002; r = −0.49, p = 0.0004; and r = −0.30, p = 0.024, respectively). E/I LF was negatively correlated with log PC20 (r = −0.30, p = 0.024). Log PC20, X5, and past smoking were identified as independent factors that affected E/I LF level. Conclusions: E/I LF as with X5 can be an indicator of central and peripheral airway obstruction in bronchial asthma patients

Airway inflammation phenotype prediction in asthma patients using lung sound analysis with fractional exhaled nitric oxide

Background: We previously reported the results of lung sound analysis in patients with bronchial asthma and demonstrated that the exhalation-to-inhalation sound pressure ratio in the low frequency range between 100 and 200 Hz (E/I LF) was correlated with the presence of airway inflammation and airway obstruction. We classified asthma patients by airway inflammation phenotype using the induced sputum eosinophil and neutrophil ratio and determined whether this phenotype could be predicted using E/I LF and fractional exhaled nitric oxide values. Methods: Steroid-naive bronchial asthma patients were classified into four phenotypes, including “Low inflammation” (35 patients), “Eosinophilic type” (58 patients), “Neutrophilic type” (15 patients), and “Mixed type” (15 patients) based on the results of induced sputum examinations. The E/I LF data and FeNO levels were then evaluated for the four phenotype groups; the prediction powers of these two indices were then analyzed for each phenotype. Results: The median E/I LF value was highest in the “Mixed type” and lowest in the “Low inflammation” group. FeNO differentiated between the “Low inflammation” and “Eosinophilic type” groups, “Low inflammation” and “Neutrophilic type” groups, and “Neutrophilic type” and “Mixed type” (p < 0.0001, p = 0.007, and p = 0.04, respectively). E/I LF differentiated between the “Low inflammation” and “Eosinophilic type” groups (p = 0.006). E/I LF could distinguish the “Mixed type” group from the “Low inflammation” and “Eosinophilic type” groups (p = 0.002). Conclusions: A combination of the E/I LF value and FeNO may be useful for the classification of the airway inflammation phenotype in patients with bronchial asthma

Lung sound analysis can be an index of the control of bronchial asthma

Background: We assessed whether lung sound analysis (LSA) is a valid measure of airway obstruction and inflammation in patients with bronchial asthma during treatment with inhaled corticosteroids (ICSs). Methods: 63 good adherence patients with bronchial asthma and 18 poor adherence patients were examined by LSA, spirometry, fractional exhaled nitric oxide (FeNO), and induced sputum. The expiration-to-inspiration lung sound power ratio at low frequencies between 100 and 200 Hz (E/I LF) obtained by LSA was compared between healthy volunteers and bronchial asthma patients. Next, post-ICS treatment changes were compared in bronchial asthma patients between the good adherence patients and the poor adherence patients. Results: E/I LF was significantly higher in bronchial asthma patients (0.62 ± 0.21) than in healthy volunteers (0.44 ± 0.12, p < 0.001). The good adherence patients demonstrated a significant reduction in E/I LF from pre-treatment to post-treatment (0.55 ± 0.21 to 0.46 ± 0.16, p = 0.002), whereas the poor adherence patients did not show a significant change. The decrease of E/I LF correlated with the improvement of FEV1/FVC ratio during the ICS treatment (r = −0.26, p = 0.04). The subjects with higher pre-treatment E/I LF values had significantly lower FEV1/FVC and V50,%pred (p < 0.001), and significantly higher FeNO and sputum eosinophil percentages (p = 0.008 and p < 0.001, respectively). Conclusions: The E/I LF measurement obtained by LSA is useful as an indicator of changes in airway obstruction and inflammation and can be used for monitoring the therapeutic course of bronchial asthma patients