Post-bronchodilator Reversibility Research Articles

Association of Absolute Eosinophil Count and Post-Bronchodilator Reversibility in the Chronic Obstructive Pulmonary Disease Patients

Objective: To look for the relationship between absolute eosinophil count and post-bronchodilator reversibility in chronic obstructive pulmonary disease patients at Pak Emirates Military Hospital, Rawalpindi Pakistan.
 Study Design: Cross sectional study.
 Place and During of Study: Pulmonology Department, Pak Emirates Military Hospital Rawalpindi (PEMH) from Jul to Dec 2019.
 Methodology: The study was conducted on 150 patients suffering from chronic obstructive pulmonary disease admitted in the Medical Ward or reporting in the Outpatient Department. Lung function was assessed using spirometry pre- and postbronchodilation. The presence and severity of chronic obstructive pulmonary disease were assessed using modified Global Obstructive Lung Disease (GOLD) criteria. The presence of significant bronchodilator responsiveness was taken as ≥12% improvement in the forced expiratory volume (FEV) (1) or the forced vital capacity.
 Results: Of 150 patients in the final analysis, 95 (63.3%) were male, and 55(36.7%) were female. The mean duration of COPD in our target population was 9.13±1.23 years. 68 (45.3%) had >12% improvement after bronchodilator administration, while 82(54.7%) had <12% improvement. The absolute eosinophilic count was <2% in 49(32.7%), while it was raised in 101(67.3%) patients. 
 Conclusion: Raised eosinophilic count emerged as a predictor of good response after administering bronchodilators among patients suffering from chronic obstructive airway disease. Screening patients for this simple blood component may predictresponse to the initial treatment and help in the tailoring of the treatment plan by the treating physician.Keywords: Chronic obstructive pulmonary disease, Eosinophils, Forced expiratory volume.

"Study on factors associated with post bronchodilator reversibility among patients presenting with dyspnea".

"Study on factors associated with post bronchodilator reversibility among patients presenting with dyspnea".

Study on Asthma and Chronic Obstructive Pulmonary Disease Overlaps among Patients with Obstructive Airway Diseases

Background and Aim: Although asthma and chronic obstructive pulmonary disease (COPD) are clinically distinct diseases, they represent biologically diverse and overlapping clinical entities and it has been observed that they often co-occur. Some research and theorizing suggest there is a common comorbid condition termed asthmachronic obstructive pulmonary disease overlap (ACO). However, the existence of ACO is controversial.Material and Methods: This is prospective, observational and descriptive study conducted at tertiary care institute of Gujarat for the duration of 1 year. Among chronic airway diseases who were classified into three groups (COPD, asthma and ACO). Patients with COPD and ACO were diagnosed according to GOLD guidelines 2020 and patients with asthma were diagnosed according to Global Initiative for Asthma (GINA) guidelines 2020. Total 150 participants were included in the research. All patients are subjected to full history taking, clinical examination, full laboratory examinations, chest radiography, spirometry and post bronchodilator reversibility test was performed and sputum analysis, where induction of sputum by hypertonic saline or mannitol is done by a trained staff with strict airborne respiratory precautions.Results: We found that 71.42% of ACO group, 79.48% of asthma group and 25% of COPD group had a positive history of atopy. Comparison of study groups regarding sputum eosinophils revealed that 30.15 % of ACO group, 76.92% of asthma group and 31.25% of COPD group had positive sputum eosinophils.Conclusion: ACO addresses an enormous rate among patients with obstructive airway diseases. It shares a few highlights of asthma like atopy and positive sputum eosinophilia, and a few highlights of COPD like old age of shows and positive smoking history

Sensitivity of FEV1 and Clinical Parameters in Children With a Suspected Asthma Diagnosis

Asthma is the most common chronic disease in children and a robust diagnosis is crucial to optimize patient care and reduce its burden. To diagnose asthma in children, the Global Initiative for Asthma (GINA) recommendations propose a 12% improvement in forced expiratory volume in 1 second (FEV1) after a bronchodilation test. Nevertheless, such a criterion is rarely confirmed in these patients in clinical practice. The objective of this study was to evaluate the sensitivity of spirometric and clinical parameters in identifying children with possible asthma. The VERI-VEMS Study is a multicenter international retrospective cohort study. Data were collected, from January 2008 until January 2019, for all consecutive children (aged 5-18 years), with a diagnosis of asthma, who performed a spirometry at the time of the diagnosis. We compared the sensitivity of the reversibility criterion proposed by GINA guidelines, with other spirometric and clinical variables, using physician-diagnosed asthma and response to treatment as the standard. The study included 871 children. The reversibility criterion of 12% of FEV1 showed a sensitivity of 30.4%. The 3 best spirometric or clinical criteria were the presence of dry cough, or wheezing or atopy and dry cough, or wheezing or exercise-induced dyspnea, with a sensitivity reaching 99.5%, with no added value of the spirometric parameters in the calculation of the cumulated sensitivity for the diagnosis of pediatric asthma. Postbronchodilator reversibility of 12%, although essential for patients' follow-up, has an insufficient low sensitivity in reaching a diagnosis of asthma in pediatric patients, compared with a combination of clinical symptoms, that show a better sensitivity. Further studies on specificity will help clarify the role of this change in the diagnostic paradigm in formally diagnosing children with asthma.

Study on factors associated with post bronchodilator reversibility among patients presenting with dyspnea: An experience at a tertiary care academic hospital in Kerala.

Background:The change in FEV1 after administration of a short-acting bronchodilator has been widely used for diagnosis of obstructive airway diseases. Many factors can influence the post bronchodilator reversibilityAim:The aim of the present study was to estimate the presence of reversibility among the patients of obstructive airway disease and to identify the factors affecting itMethods:Patients who presented to the department of respiratory medicine with symptoms of dyspnea were evaluated with spirometry. Spirometry and post bronchodilator reversibility (BDR) was defined as per international guidelines. SPSS 17 was used for statistical analysis and P < 0.05 was considered significantResults:Out of 100 patients studied, 33 had BDR. Median age of the population was 58 ± 17 years. There were 72 non-smokers and 58 men. A total of 32 had chronic obstructive pulmonary disease (COPD), 56 had asthma, and 12 had normal spirometry. The median pre and post bronchodilator FEV1 was 1.34L/Sec and 1.46 L/sec respectively. Twenty-seven of asthma (41%) and 6 of COPD (19%) had BDR (P = 0.05). Other factors associated with BDR were smoking (P = 0.035). There was no statistically significant correlation found between eosinophilia, gender, severity of obstruction, BMI, height, weight and ageConclusion:The prevalence of post BDR in the study population was 33%. The factors affecting BDR were smoking status, and asthma. The study did not show any significant correlation between BDR and eosinophilia, gender, height and age.

Oscillometry – The future of estimating pulmonary functions

The prevalence of asthma is increasing rapidly, worldwide, due to changing gene-environment interactions. The rate of rise is more in resource poor nations due to lack of knowledge and non-availability of expertise. Monitoring of lung functions is mandatory for diagnosis and further management of asthmatic patients. Spirometry, the widely available investigation, is the gold standard test used for mapping pulmonary dynamicity. It has got its own limitations in the form of operational difficulties in children, the elderly, and in those with neuromuscular or behavioral issues. In the current era of COVID-19 pandemic, the utility of spirometry has been further restricted to selected cohort only, due to potential risk of viral transmission during the procedure. Oscillometry technique has been used previously, to monitor lung functions, with promising results. Ultrasonic waves of various frequencies accompany the tidal breath of patients and respiratory impedance is calculated by measured pressure and flow signals from exhaled breath. The results are interpreted in the form of resistance, reactance, resonant frequency, and reactance area. Various manufacturers have developed different mechanical models with slight variation in impulse pattern till date. There are certain distinct advantages of oscillometry over spirometry. Being tidal breath-based maneuver, it is more child friendly. People with neuromuscular weakness, cognitive limitations, and the elderly can easily perform it with only minor understanding and effort. Oscillometry is more sensitive than spirometry in detecting peripheral airway diseases. Post-bronchodilator reversibility can be evaluated by comparing with the baseline respiratory characteristics. Their utility in restrictive diseases and vocal cord dysfunction has also been explored. Less aerosol generation during the normal tidal breath is another advantage of oscillometry, over spirometry needing forceful efforts, which makes it more suitable for use in viral pandemic situations for monitoring patients with both asthma and pneumonia. More research is needed, in various geographic locations and heterogeneous populations, to devise the normative data of oscillometric parameters. Simultaneously, there is an urgent need for standardization of available machines at global platform.

Evaluation of Post-Bronchodilator Reversibility in Patient with Chronic Obstructive Pulmonary Disease and Asthma

Obstructive lung disease is a group of disorders comprising Chronic Obstructive Pulmonary Disease (COPD) and asthma. It is one of the most common causes of morbidity and mortality worldwide. COPD is a preventable and treatable disease characterized by persistent respiratory symptoms and airflow limitation, whereas asthma is reversible episodes of recurrent wheezing, cough, breathlessness, and chest tightness. It is sometimes difficult to distinguish COPD from asthma when COPD patients present with significant post-bronchodilator reversibility. Spirometry is the gold standard test to diagnose obstructive airway disease. We carried out a hospital-based cross-sectional study in Nepal Medical College Teaching Hospital from January 2018 to December 2018. One hundred and ninety eight patients who met the inclusion criteria underwent spirometry. Basal and post-bronchodilator FEV1, FVC, FEV1/FVC, and reversibility of FEV1 were measured. The majority of the patients enrolled in the study were males (n=100). The mean age of the patients was 49.3±17.0 years. Most of the patients were above 60 years of age (n=68). Clinical diagnosis of asthma was made in 113 (57%) and COPD in 85 (43%) patients. Post-bronchodilator reversibility was observed in 48 (42%) asthmatic and 19 (22%) COPD patients. Post-bronchodilator reversibility was statistically significant in asthmatic patients (p=0.032). Post-bronchodilator reversibility was observed in COPD patients as well. Therefore, post-bronchodilator reversibility alone may have a limited role in differentiating COPD from bronchial asthma. However, spirometry is mandatory to diagnose a patient with obstructive lung disease.

Assessment of severity of sleep apnea in obstructive airway diseases patients at tertiary care hospital

Obstructive sleep apnea if remains untreated can lead to excessive daytime sleepiness, diminished performance and overall poor quality of life. Factors that increase vulnerability of sleep apnea include age, male sex, obesity, family history, craniofacial abnormalities and certain health behaviors such as alcohol abuse and smoking. Previously diagnosed cases of COPD and bronchial asthma (as per guidelines) having symptoms of obstructive sleep apnea were also included in this study. This present study was planned to study assessing of severity of sleep apnea in obstructive airway diseases patients.The present study was conducted in sleep laboratory of the Department of Pulmonary Medicine of a tertiary care hospital that caters to population of diverse groups. Patients after clinical examination and spirometry with post bronchodilator reversibility were categorized into bronchial asthma and COPD. Subsequently, polysomnography was done of these patients to study the sleep pattern. Amongst patients with COPD, 11 (16.42%) had mild COPD, 26 (38.80%) had moderate COPD, 22 (32.84%) had severe COPD and 08 (11.94%) patients had very severe COPD. 38.71% and 29.03% that is 12 and 09 out of 31 patients had moderate and severe asthma respectively. Again 19.36% and 12.90% that is 06 and 04 patients had mild persistent and intermittent asthma respectively. 17(25.37%) patients of COPD were found to have obstructive sleep apnea and 09 (29.03%) patients of asthma had obstructive sleep apnea. In patients with overlap syndrome had more severe hypercapnia (mean PaCO 48.88 ±0.017), and nocturnal desaturation (mean 85.35% ±0.022) Patients having moderate COPD had severe OSA. Patients having severe asthma had severe OSA with correlation coefficient R = -0.527 with p value &amp;#60;0.001 meaning negative linear correlation between AHI and % FEV1 of predicted of asthma patients.

Study of sleep patterns in asthma and COPD diseases at tertiary care hospital in India

Sleep is the natural periodic suspension of consciousness during which the powers of the body are recovered. It is a natural periodic state of rest for the mind and body, in which the eyes usually close and consciousness is completely or partially lost so that there is a decrease in bodily movement and responsiveness to external stimuli. Present study was planned to study the sleep patterns in various respiratory diseases at Tertiary care Hospital in India.The present study was conducted in sleep laboratory of the Department of Pulmonary Medicine of a tertiary care hospital that caters to population of diverse groups. Patients after clinical examination and spirometry with post bronchodilator reversibility were categorized into bronchial asthma and COPD. Subsequently polysomnography was done of these patients to study the sleep pattern. Total sleep time appears to be decreased in COPD patients with mean value of 284.3 (± 43.02) minutes, with decreased sleep efficiency of 66.64 % (± 0.074). Study group patients have frequent awakenings with average of 17.73 (± 6.15). They have decreased slow wave sleep (S3 and S4 stages) with mean value for S3 is 2.81% (± 0.68) and for S4 is 6.45% (± 1.64). The mean value for REM sleep in these patients is 12.42% (± 2.72) and that for S1 and S2 is 13.99% (± 4.84) and 64.62% (± 4.72) respectively. Total sleep time appears to be decreased in asthmatic patients with mean value of 299.89 (± 45.17) minutes, with decreased sleep efficiency of 68.38% (± 0.065). Study group patients have frequent awakenings with average of 21.03% (± 7.44). In patients with Asthma &amp; COPD, polysomnography study suggests poor sleep quality characterized by decreased total sleep time, decreased sleep efficiency, frequent awakenings, altered sleep architecture with decreased slow wave sleep and REM sleep.

Variation in spirometry parameters in children with and without recurrent respiratory problems

Background: Children having recurrent episodes of respiratory symptoms account for a major source of hospitalization. These children have increased morbidities and if not identified in time can have impaired lung function as adults. &#x0D; Objectives: The aim of our study was to compare the spirometry parameters and bronchodilator reversibility in children with and without recurrent respiratory problems.&#x0D; Methodology: This was a prospective observational study conducted in the Pediatric department of Manipal Teaching Hospital comparing 35 children with recurrent respiratory problems and 35 children with no history of recurrent respiratory problems. After thorough instructions, baseline spirometry was done in all children and recordings were noted. Thereafter they were given two puffs of salbutamol (100 µg) and repeat testing was done 20 minutes later. Bronchodilator reversibility was calculated according to standard formula. Various statistical tests were used to compare the findings between the two groups.&#x0D; Results: The recurrent respiratory problem group had 31 (88%) cases of bronchial asthma, two (5.7%) bronchiolitis obliterans, one (2.8%) pulmonary eosinophilia, and one (2.8%) common variable immunodeficiency syndrome. The median values of FEV1 (p=&lt;0.001), FVC (p=0.007), FEV1/FVC (p=0.005), PEF (p=0.042) and FEF25-75(p=0.026) were lower in the group with recurrent respiratory problems. Post-bronchodilator reversibility of FEV1 (p=0.001), FVC (p=&lt;0.001) and FEF25-75 (p=0.026) was higher in the groups with recurrent respiratory problems&#x0D; Conclusion: We found that lung function parameters in children with recurrent respiratory problems show features of obstructive defect. The post-bronchodilator response is higher in the group with recurrent respiratory problems as compared to normal children.

Identification and definition of asthma-COPD overlap: The CanCOLD study.

Lack of consensus on diagnosis of ACO limits our understanding of the impact, management and outcomes of ACO. The present observational study aims to describe the prevalence, clinical characteristics and course of individuals with ACO based on various definitions used in clinical practice. We included individuals with COPD from the prospective, multisite CanCOLD study and defined subjects with ACO using seven definitions commonly used in the literature. Data including questionnaires, lung function and CT scans were analysed from 522 individuals with COPD who were randomly recruited from the population. Among them, 264 fulfilled at least one of the seven definitions of ACO. Prevalence of ACO varied from 3.8% to 31%. Regardless of the definition, individuals with ACO had worse outcomes (lung function and higher percentage of fast decliners, symptoms and exacerbations, health-related quality of life and comorbidities) than the remaining patients with COPD. Conversely, patients with non-ACO had higher emphysema and bronchiolitis scores. The three definitions that included atopy and/or physician diagnosis of asthma identified subjects who differed significantly from patients with COPD. The two ACO definitions with post-bronchodilator reversibility were concordant with COPD and were the least stable, with less than 50% of the patients from each group maintaining reversibility over visits. Atopy and physician-diagnosed asthma are more distinguishing characteristics to identify ACO. This finding needs to be validated using measures of airway inflammation and other specific biomarkers.

Children with uncontrolled asthma and significant reversibility might show hypoxaemia.

Asthmatic children free of exacerbation with airway obstruction may have low partial pressure of oxygen (PaO2) which can be a marker for future risk, but PaO2 is scarcely measured during pulmonary function testing. We prospectively included asthmatic children with airway obstruction referred for pulmonary function testing, including blood gas analysis (n = 51). Hypoxaemia, defined as a value lower than - 2 z-score, was present in 15 (29%) children, and 37 (72%) children had a significant reversibility after bronchodilator administration. The multivariable model showed a positive influence of baseline forced expiratory volume in 1s (FEV1) on PaO2 (β coefficient 0.69, [95% CI: 0.07; 1.30]; P = 0.03), whereas uncontrolled asthma and FEV1 reversibility negatively influenced it (β coefficient - 1.59 [95% CI: - 2.74; - 0.44]; P = 0.01; and - 0.07 [95% CI: - 0.13; - 0.02]; P = 0.01, respectively). As a consequence, children with uncontrolled symptoms of asthma and FEV1 reversibility ≥ 12% were significantly more at risk of having hypoxaemia compared to children with well/partly controlled asthma or no significant reversibility of FEV1.Conclusion: Among obstructive asthmatic children without current exacerbation, hypoxaemia is more likely to be seen in children with uncontrolled asthma and a significant post-bronchodilator FEV1 reversibility, in favour of different pathophysiology and treatment requirements of their airway obstruction.What is Known:• Recommendations are to treat asthmatic children in order to control respiratory symptom and maintain normal pulmonary function.• Asthmatic children free of exacerbation may have different pathophysiology for airway obstruction (central, peripheral, inflammatory, spasticity, remodelling) and should be treated according the pathophysiology of their airway disease.What is New:• In obstructive asthmatic children free of current exacerbation, the presence of hypoxaemia (ventilation-perfusion mismatch) is influenced by asthma control and post-bronchodilator reversibility, independently of the level of baseline airway obstruction.• The presence of hypoxaemia in obstructive asthmatic children free of current exacerbation can be highly suspected by the composite index "uncontrolled asthma + FEV1reversibility ≥ 12%" which may guide treatment.

Bronchodilator reversibility: What are the differences between asthma and chronic obstructive pulmonary disease?

INTRODUCTION: Currently, the bronchodilator reversibility is not recommended to differentiate asthma from chronic obstructive pulmonary disease (COPD); however, physiopathological specificities of each disease contribute to the differences in response to the drug. OBJECTIVES: The objective of this study is to evaluate the differences in bronchodilator response between asthmatic and COPD patients and to determine which of the bronchodilation criteria have the best ability to detect the positive response in these patients. MATERIALS AND METHODS: This was a cross-sectional study. The sample included 104 patients with asthma or COPD who performed lung function tests between January and March 2018. The whole sample was analyzed according to postbronchodilator variation (Δ) of lung function parameters, and the postbronchodilator reversibility was characterized using a multiple bronchodilation criteria. The drug used in reversibility test was salbutamol. RESULTS: In this study, Δ forced-expiratory volume in the 1st s (ΔFEV1) and a Δ Raw was statistically higher in the group with asthma compared with the group with COPD. In the asthma group, the criteria ↓ functional residual capacity (FRC) ≥10%, ↓Raw ≥ 35%, ↑ forced expiratory flow between 25% and 75% of vital capacity (FEF25%–75%) ≥20% and ↑ FEV1 and / or ↑ forced vital capacity ≥12% and 200 mL were those that presented a greater capacity of detecting a positive response to bronchodilator. The criteria ↑ FEF25%–75%≥20% and ↓ FRC ≥ 10% were those that had the greater ability of detecting airway reversibility in COPD group. CONCLUSION: The analysis of postbronchodilator FEV1 and raw modifications as well as the using of a combination of multiple bronchodilation criteria contribute to a deeper characterization of bronchodilator reversibility in asthma and COPD.

Hyperpolarized Helium 3 MRI in Mild-to-Moderate Asthma: Prediction of Postbronchodilator Reversibility.

Background Longitudinal progression to irreversible airflow limitation occurs in approximately 10% of patients with asthma, but it is difficult to identify patients who are at risk for this transition. Purpose To investigate 6-year longitudinal changes in hyperpolarized helium 3 (3He) MRI ventilation defects in study participants with mild-to-moderate asthma and identify predictors of longitudinal changes in postbronchodilator forced expiratory volume in 1 second (FEV1) reversibility Materials and Methods Spirometry and hyperpolarized 3He MRI were evaluated in participants with mild-to-moderate asthma in two prospectively planned visits approximately 6 years apart. Participants underwent methacholine challenge at baseline (January 2010 to April 2011) and pre- and postbronchodilator evaluations at follow-up (November 2016 to June 2017). FEV1 and MRI ventilation defects, quantified as ventilation defect volume (VDV), were compared between visits by using paired t tests. Participants were dichotomized by postbronchodilator change in FEV1 at follow-up, and differences between reversible and not-reversible groups were determined by using unpaired t tests. Multivariable models were generated to explain postbronchodilator FEV1 reversibility at follow-up. Results Eleven participants with asthma (mean age, 42 years ± 9 [standard deviation]; seven men) were evaluated at baseline and after mean 78 months ± 7. Medications, exacerbations, FEV1 (76% predicted vs 76% predicted; P = .91), and VDV (240 mL vs 250 mL; P = .92) were not different between visits. In eight of 11 participants (73%), MRI ventilation defects at baseline were at the same location in the lung at follow-up MRI. In the remaining three participants (27%), MRI ventilation defects worsened at the same lung locations as depicted at baseline methacholine-induced ventilation. At follow-up, postbronchodilator FEV1 was not reversible in six of 11 participants; the concentration of methacholine to decrease FEV1 by 20% (PC20) was greater in FEV1-irreversible participants at follow-up (P = .01). In a multivariable model, baseline MRI VDV helped to predict postbronchodilator reversibility at follow-up (R 2 = 0.80; P < .01), but PC20, age, and FEV1 did not (R 2 = 0.63; P = .15). Conclusion MRI-derived, spatially persistent ventilation defects predict postbronchodilator reversibility 78 months ± 7 later for participants with mild-to-moderate asthma in whom there were no changes in lung function, medication, or exacerbations. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Stojanovska in this issue.

Subterranean Pulmonary Rehabilitation in Chronic Obstructive Pulmonary Disease.

Pulmonary rehabilitation (PR) has been recommended as an integral part of treatment for patients with chronic obstructive pulmonary disease (COPD). Climate therapy in salt mine chambers has been found of benefit in chronic respiratory diseases. The study compares long-term effects of underground PR in the Wieliczka Salt Mine with that conducted on the surface. There were 42 COPD patients enrolled in the study, with FEV1/FVC <0.7 predicted and post-bronchodilator reversibility <12%, randomized into pulmonary rehabilitation in the mine (Group I, n=23) and PR on the surface (Group II, n=19). The outcomes consisted of lung function variables, exercise performance (6-min walk test - 6MWT), dyspnea (mMRC), and compliance with the disease and quality of life (COPD Assessment Test - CAT) and BODE index, compared at baseline (P0), end (P1), and 6months after pulmonary rehabilitation (P2). The findings were that subterranean pulmonary rehabilitation significantly reduced CAT score (p<0.001), BODE index (p=0.004), and dyspnea (mMRC) (p=0.001) and increased distance in 6MWT (p<0.001), compared with its equivalent conducted on the surface. Further, beneficial effect of subterranean treatment was sustained during the following half a year as opposed to the effect noticed on patients treated on the surface. We conclude that subterranean pulmonary rehabilitative treatment reduces symptoms and improves exercise tolerance to a greater and sustained extent, compared to a similar treatment on the surface, in patients suffering from COPD.

Évolution respiratoire à moyen et long terme des enfants opérés d’une hernie diaphragmatique congénitale : à partir d’une série de 56 patients

Recent advances in prenatal diagnosis, high frequency oscillatory ventilation and pulmonary arterial hypertension (PAH) therapies have progressively improved the survival of patients with congenital diaphragmatic hernia (CDH). However, CDH is associated with high morbidity that affects about half of surviving children. The main sequelae observed are respiratory (asthma, persistent PAH [PPAH], bronchopulmonary dysplasia, respiratory infections) and digestive (gastroesophageal reflux disease [GERD]). This retrospective study focuses on the medium and long-term respiratory evolution of a cohort of 56children with CDH and operated at Strasbourg University Hospital between 1999and 2017. The mean age at assessment was 6,6years (minimum: 5months; maximum: 19years). Seventeen patients (30%) had asthmatic manifestations. Pulmonary Function Tests (PFT) showed obstructive patterns in 5/11patients (2with post-bronchodilator reversibility), and restrictive impairment in 5/11patients, 3of whom had thoracic deformity and/or scoliosis. Thirteen patients (23%) had bronchopulmonary dysplasia. Few patients had recurrent respiratory infections (3.6%) and chronic respiratory insufficiency (5.3%). Thirty-nine patients (70%) presented with an initial PAH, two of whom progressed to PPAH. Sixteen patients (29%) had thoracic deformity and/or scoliosis and 48patients (86%) had GERD, 10of whom had fundoplication. The long-term respiratory outcome of CDH operated patients is characterized by a moderate prevalence of respiratory symptoms and alterations in PFT that are important to consider in their medical follow-up during adolescence and adulthood. PAH is common in the neonatal period but rarely seems to persist.

Post-bronchodilator Reversibility of FEV1 and Eosinophilic Airway Inflammation in COPD

IntroductionThe relationship between bronchodilator responsiveness and eosinophilic airway inflammation has not been well documented in COPD. It has been investigated in this retrospective study. This issue has grown in importance due to increasing interest in the asthma-COPD overlap syndrome. Methods264 stable COPD patients with no past history of asthma were retrospectively analyzed. Correlation analyses between FEV1 reversibility and sputum eosinophil levels were conducted. Sputum eosinophil levels were dichotomized using FEV1 reversibility cut-off points (>0.4L and >15% vs. >0.2L and >12%) and compared. The effectiveness of FEV1 reversibility to predict sputum eosinophilia (>3%) was analyzed with a logistic regression and a ROC analysis. Results82 (31.1%) patients with higher FEV1 reversibility values (0.14 vs. 0.11L, P=.01) presented sputum eosinophilia. FEV1 reversibility was weakly correlated with the sputum eosinophil level (r=0.162, P=.008). Patients with FEV1>0.4L and >15% increment had higher sputum eosinophil levels (6.11 vs. 1.02%, P=.049) whereas the level did not differ when dichotomized by FEV1 increment >0.2L and >12%. Very positive FEV1 reversibility (>0.4L and >15%) predicted sputum eosinophilia after adjustment forage, baseline FEV1 and FVC (OR: 4.262, P=.029). In the ROC analysis, the AUC was 0.58 (P=.034), and FEV1 increment>0.4L and >15% had a positive predictive value of 63.6% and an overall accuracy of 70.1%. ConclusionsFEV1 reversibility was weakly correlated with sputum eosinophil levels in COPD. Positive FEV1 reversibility (>0.4L and >15%) is moderately successful in predicting sputum eosinophilia (>3%).

Benralizumab for patients with mild to moderate, persistent asthma (BISE): a randomised, double-blind, placebo-controlled, phase 3 trial

Benralizumab is a humanised, anti-interleukin 5 receptor α monoclonal antibody that directly and rapidly depletes eosinophils, reduces asthma exacerbations, and improves lung function for patients with severe eosinophilic asthma. The objective of this trial was to assess the safety and efficacy of benralizumab for patients with mild to moderate, persistent asthma. In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients aged 18-75 years, weighing at least 40 kg, and with a postbronchodilator reversibility in forced expiratory volume in 1 s (FEV1) of at least 12% at screening, from 52 clinical research centres in six countries. Patients must have been receiving either low- to medium-dosage inhaled corticosteroids (ICS) or low-dosage ICS plus long-acting β2 agonist fixed-combination therapy at screening, had a morning prebronchodilator FEV1 of more than 50% to 90% predicted at screening, and had one or more of the following symptoms within the 7 days before randomisation: a daytime or night-time asthma symptom score of at least 1 for at least 2 days, rescue short-acting β2 agonist use for at least 2 days, or night-time awakenings due to asthma for at least one night. We converted patients' ICS treatments to 180 μg or 200 μg budesonide dry powder inhaler twice daily for the entire duration of the study using the approved dosages in the patients' respective countries and randomly allocated them (1:1; stratified by blood eosinophil count [<300 cells per μL vs ≥300 cells per μL] and region [USA vs the rest of the world]) with an interactive web-based voice response system to receive subcutaneous placebo or benralizumab 30 mg injections every 4 weeks for 12 weeks. All patients and investigators involved in patient treatment or clinical assessment and those assessing outcomes were masked to treatment allocation. The primary endpoint was change from baseline prebronchodilator FEV1 at week 12. Efficacy analyses used an intention to treat approach. This trial is registered with ClinicalTrials.gov, number NCT02322775. Between Feb 2, 2015, and April 24, 2015, we enrolled 351 patients, with 211 (60%) randomly assigned (105 [50%] to placebo and 106 [50%] to benralizumab). Benralizumab resulted in an 80 mL (95% CI 0-150; p=0·04) greater improvement (least-squares mean difference) in prebronchodilator FEV1 after 12 weeks than did placebo (placebo group: 2246 mL [SD 768] at baseline vs 2261 mL [796] at week 12, change from baseline of 0 mL; benralizumab group: 2248 mL [606] vs 2310 mL [670], 70 mL). 44 (42%) patients in the benralizumab group had adverse events compared with 49 (47%) in the placebo group. The most common adverse events for both groups were nasopharyngitis (eight [8%] patients in each group) and upper respiratory tract infections (five [5%] patients in each group). Serious adverse events occurred in two (2%) patients each in the benralizumab (pancytopenia and a suicide attempt, both considered unrelated to treatment) and placebo (cervix carcinoma and colon adenoma) groups. This study suggests that active and modifiable disease processes might be ongoing in patients with mild to moderate, persistent asthma receiving ICS. Although the lung function improvement observed does not warrant use of benralizumab in this population because it did not reach the minimum clinically important difference of 10%, further studies to assess this finding should be considered. AstraZeneca.

Post-bronchodilator Reversibility of FEV1 and Eosinophilic Airway Inflammation in COPD

IntroductionThe relationship between bronchodilator responsiveness and eosinophilic airway inflammation has not been well documented in COPD. It has been investigated in this retrospective study. This issue has grown in importance due to increasing interest in the asthma-COPD overlap syndrome. Methods264 stable COPD patients with no past history of asthma were retrospectively analyzed. Correlation analyses between FEV1 reversibility and sputum eosinophil levels were conducted. Sputum eosinophil levels were dichotomized using FEV1 reversibility cut-off points (>0.4L and >15% vs. >0.2L and >12%) and compared. The effectiveness of FEV1 reversibility to predict sputum eosinophilia (>3%) was analyzed with a logistic regression and a ROC analysis. Results82 (31.1%) patients with higher FEV1 reversibility values (0.14 vs. 0.11L, P=.01) presented sputum eosinophilia. FEV1 reversibility was weakly correlated with the sputum eosinophil level (r=0.162, P=.008). Patients with FEV1>0.4L and >15% increment had higher sputum eosinophil levels (6.11 vs. 1.02%, P=.049) whereas the level did not differ when dichotomized by FEV1 increment >0.2L and >12%. Very positive FEV1 reversibility (>0.4L and >15%) predicted sputum eosinophilia after adjustment forage, baseline FEV1 and FVC (OR: 4.262, P=.029). In the ROC analysis, the AUC was 0.58 (P=.034), and FEV1 increment>0.4L and >15% had a positive predictive value of 63.6% and an overall accuracy of 70.1%. ConclusionsFEV1 reversibility was weakly correlated with sputum eosinophil levels in COPD. Positive FEV1 reversibility (>0.4L and >15%) is moderately successful in predicting sputum eosinophilia (>3%).

Serum levels of IL-10, IL-17F and IL-33 in patients with asthma: a case–control study

Objectives: The development of inflammation in asthma involves an intricate network of cytokines that recruit and activate numerous immune cells. This study was aimed to compare serum levels of IL-10, IL-17F, and IL-33 in asthmatic patients and non-asthmatic controls and correlate cytokine levels to asthma severity and various clinical, spirometric, and laboratory variables. Methods: Using ELISA, serum levels of IL-10, IL-17F, and IL-33 were evaluated in 44 asthmatics (14 mild persistent, 15 moderate persistent, and 15 severe persistent) and 44 controls. Results: This is one of the first reports showing a significant difference in serum levels of asthma-associated cytokines, anti-inflammatory IL-10, and pro-inflammatory IL-17F and IL-33, in the same subset of asthmatic patients. Our results showed diminished level of IL-10 and elevated levels of IL-17F and IL-33 in asthmatics than in controls (p < 0.001). Assessment of cytokine levels between subjects of different gender, age group, and BMI showed non-significant differences. Correlation analysis of cytokine levels to clinical variables showed that IL-17F is associated negatively to FVC % predicted (forced vital capacity) and FEV1% predicted (forced expiratory volume in one second) and positively to number of allergens sensitized and FEV1 reversibility. A strong negative correlation was found between IL-10 and IL-33 levels (p = 0.001). Conclusions: Negative correlation between IL-10 and IL-33 levels may reflect a converse relationship between anti-inflammatory and pro-inflammatory cytokines in an individually balanced pattern. The association between IL-17F level and asthmatic phenotypes such as reduced FVC and FEV1, higher degree of sensitization, and post-bronchodilator reversibility needs further assessments.