Use Of Bronchodilators Research Articles

Journal Club - Endobronchial Valve Bronchoscopic Lung Volume Reduction.

It is estimated that approximately 3.5 million American adults have been diagnosed with emphysema, an irreversible destruction of the alveolar lung parenchyma. In advanced cases, the lung damage is so severe that significant air trapping occurs and does not improve with the use of bronchodilators and other conventional medicines used for chronic obstructive pulmonary disease (COPD). Viable surgical options include bullectomy, lung volume reduction surgery (LVRS), and lung transplantation but many patients may not be appropriate candidates for these procedures and/or there are long wait times for transplantation. Recently, the U.S. Food and Drug Administration (FDA) approved the Zephyr® endobronchial valve (EBV) (Zephyr Valve EBV; Pulmonx Corporation, Redwood City, California) for bronchoscopic lung volume reduction for patients with severe emphysema who are not responsive to medical therapy. This 1-way valve, the size of a pencil eraser, is inserted into the targeted diseased portion of the lung. Typically, 4 to 8 valves are inserted into the chosen emphysematous lobe and will allow air to escape out of that region but prevent any further air from entering, leading to deflation, and ultimately, total lobar collapse over a matter of weeks. An earlier study with the Zephyr® valves, the “Endobronchial Valve for Emphysema Palliation Trial, (VENT)” study,1 was a multicenter trial with 321 participants (220 with EBV insertion) that demonstrated statistically significant improvements in forced expiratory volume in 1 second (FEV1) and the 6-minute walk distance test (6MWD) between EBV and standard of care (SoC) groups but these were not clinically meaningful differences (mean change in FEV1 was 60 mL and median difference from baseline 6MWD 19.1 m).1 Post hoc analysis indicated that the best responders were those who demonstrated the following criteria: little to virtually no collateral ventilation to ipsilateral adjacent lobes, complete lobar occlusion achieved with the correct occlusive positioning of the valves in all segmental and sub-segmental airways and complete intact fissures between lobes.2,3 With this information, Pulmonx developed a unique technology-- Chartis (Pulmonx Corporation, Redwood City, California) a device that tests for collateral ventilation to judge the appropriateness of valve insertion.4 The Chartis system consists of a console connected to a balloon catheter with a central channel that is used to occlude the target lobe and to subsequently measure pressure and flow to calculate resistance to airflow and hence to quantify collateral ventilation in that lobe.4 More recently, advanced computed tomography (CT) scan analysis techniques have been developed that can virtually eliminate the need for testing with the Chartis system.5,6 Advanced CT analysis techniques have become a key element of deciding on the appropriateness of candidates. This has been confirmed with several short-term single center studies.2,7,8 The FDA actually granted the Zephyr® valve “breakthrough device” designation, allowing the FDA to provide guidance on efficient device development and to expedite evidence generation and review of the device. This designation generally signals the recognition that there are relatively few viable options for treating the targeted patient population. Indeed, the first study we review by Criner and colleagues, LIBERATE (below) is the first large, prospective, randomized controlled, multicenter study to evaluate the effectiveness, safety and durability of the benefit out to 12 months in patients with severe heterogeneous emphysema and with little to no collateral ventilation in the target lung. In order to expedite approval, the FDA required that, compared to previous studies, the primary endpoints show a greater magnitude of difference between Zephyr valve insertion and SoC versus a sham procedure and then SoC. In this Journal Club we will review this pivotal study that led to the approval of the Zephyr® valve in the United States and other recent studies that have evaluated the efficacy and safety of this device. Note: Abstracts are presented in their original, published format and have not been edited to match JCOPDF style.

Bronchiectasis in severe asthma: a distinct phenotype?

The presence of bronchiectasis has been described in about 30% of severe asthma patients. The coexistence of these two respiratory conditions poses new challenges from both clinical and research perspectives. We will review the available literature on this topic to discuss the existance of a specific clinical phenotype of asthma. Despite the paucity of literature, the presence of bronchiectasis with severe asthma is associated with older age, chronic bronchial expectoration, rhinosinusitis, more frequent and severe exacerbations, neutrophilic airway inflammation and poor response to usual treatment. Conversely, asthma features are also described in bronchiectasis patients even in the absence of an appropriate diagnosis of asthma. In both cases, there is some evidence supporting the use of bronchodilators, macrolides and respiratory physiotherapy, while the use of inhaled corticosteroids and antibiotics is controversial. Based on available evidence on the association between (severe) asthma and bronchiectasis, its pathophysiology, certain clinical aspects and prognosis are largely unclear. Although specific management appears to be required in most cases, in our opinion there is still insufficient evidence to consider it a distinct phenotype of severe asthma. Hopefully, future research will shed more light on this topic and define the best therapeutic approach.

Эффективность и безопасность применения бронходилататоров в терапии хронической сердечной недостаточности ишемического генеза в сочетании с хронической обструктивной болезнью легких

Эффективность и безопасность применения бронходилататоров в терапии хронической сердечной недостаточности ишемического генеза в сочетании с хронической обструктивной болезнью легких

Timely Data for Targeted Quality Improvement Interventions: Use of a Visual Analytics Dashboard for Bronchiolitis.

Standard methods for obtaining data may delay quality improvement (QI) interventions including for bronchiolitis, a common cause of childhood hospitalization. To describe the use of a dashboard in the context of a multifaceted QI intervention aimed at reducing the use of chest radiographs, bronchodilators, antibiotics, steroids, and viral testing in patients with bronchiolitis. This QI initiative took place at Children's Minnesota, a large, not-for-profit children's health care organization. A multidisciplinary bronchiolitis workgroup developed a local clinical guideline and order-set. Delays in obtaining baseline data prompted a pediatric hospitalist and information technology specialist to modify a vendor's dashboard to display data related to bronchiolitis guideline metrics. Patients 2 months to 2 years old with a bronchiolitis emergency department (ED)/inpatient encounter in the period October 1, 2014 to April 30, 2018 were included. The primary outcome was a functioning dashboard; a process measure was the percentage of ED clinician logins. Outcome measures included the percent use of guideline metrics (e.g., bronchodilators) displayed on statistical process control charts (ED vs. inpatient). Balancing measures included length of stay, charge ratios, and hospital revisits. A workgroup (formed October 2015) implemented a bronchiolitis order-set and guideline (February 2016) followed by a bronchiolitis dashboard (August 2016) consolidating disparate data sources loaded within 2 to 4 days of discharge. In total, 35% of ED clinicians logged in. Leaders used the dashboard to target and track interventions such as a bronchodilator order alert. There were improvements in most outcome metrics; however, timing did not suggest direct dashboard impact. ED balancing measures were lower after implementation. We described use of a dashboard to support a multifaceted QI initiative for bronchiolitis. Leaders used the dashboard for targeted interventions but the dashboard did not directly impact the observed improvements. Future studies should assess reasons for low individual dashboard use.

Эффективность и безопасность длительного применения пролонгированных бронходилататоров у больных с кардиопульмональной патологией и хронической сердечной недостаточностью

Эффективность и безопасность длительного применения пролонгированных бронходилататоров у больных с кардиопульмональной патологией и хронической сердечной недостаточностью

Impact of a new acute bronchiolitis protocol on clinical practice

IntroductionThe prevalence and the variability of clinical practice in acute bronchiolitis make it a perfect candidate to monitor the proper use of resources. The aim of this study is to analyse the differences in the use of non-recommended resources in the management of bronchiolitis in the Emergency Department, before and after the establishment of a new protocol. MethodsA retrospective study was conducted on a sample of patients diagnosed with acute bronchiolitis in the Emergency Department of a tertiary hospital, before (December 2014) and after (December 2016) the implementation of a new protocol. A comparison was made on the use of diagnostic tests and treatments in both groups. ResultsThe analysis included a total of 113 patients with acute bronchiolitis examined in December 2014, and 128 patients in December 2016. The clinical characteristics in both groups were similar. In the post-protocol period, there was a significant decrease in the use of salbutamol, both in the Emergency Department (33.6% vs 19.5%, P<.01) and at discharge (46.7% vs 15.2%, P<.001); adrenaline (12.4% vs 2.4%, P=.002); and nebulised hypertonic saline solution (5.3% vs 0.8%, P=.04). Rapid respiratory syncytial virus (RSV) testing was also decreased (40.7% vs 26.6%, P=.01). This decrease was not associated with an increase in the number of admissions or re-assessments in the Emergency Department. ConclusionsThe establishment of a new protocol for acute bronchiolitis decreased the use of non-recommended resources, mainly the use of bronchodilators and rapid RSV testing.

Dynamic tonsillar prolapse masquerading as paradoxical vocal fold movement dysfunction

IntroductionParadoxical vocal fold movement dysfunction (PVFMD) is a disorder in which the vocal folds involuntarily adduct during inspiration resulting in stridor, cough, dysphonia and dyspnea. Diagnosis of PVFMD is difficult given the episodic nature of the disorder and the often-normal laryngeal exam in between episodes. Moreover, additional sources of obstruction have been identified as sources of Periodic Occurrence of Laryngeal Obstruction (POLO). Treatments can vary with site of obstruction. ObjectiveTo evaluate pediatric patients presenting to a Vocal Fold Dysfunction Center for evaluation of exertional, inspiratory, harsh breath sounds and dyspnea suggestive of PVFMD whom were found to have a dynamic obstruction of the upper airway due to adenotonsillar hypertrophy and prolapse. MethodsRetrospective chart review of patients diagnosed with exertional dynamic tonsillar prolapse whom have undergone adenotonsillectomy. Clinical characteristics, spirometry, exam findings and response to adenotonsillectomy were recorded. ResultsSeven patients with exercise induced dyspnea and respiratory distress with whom underwent exercise spirometry then subsequent adenotonsillectomy were identified. Symptomatic co-morbidities were common and included: rhinitis (43%), reflux (29%), sleep disordered breathing (29%), asthma (14%), obesity (14%), prematurity (14%) and anxiety/post-traumatic stress disorder (PTSD) (14%). Preoperative use of bronchodilators or reflux medications was common. All patients were noted to have >50% oropharyngeal obstruction secondary to tonsillar hypertrophy and dynamic lateral pharyngeal collapse or tonsillar prolapse with inspiration. No exercise induced paradoxical vocal fold dysfunction was identified. All baseline and most exertion FVC, FEV1, FEV1/FVC and FEF 25–75% were normal. Four patients had flow volume loops suggestive of obstruction. All patients had symptomatic improvement after adenotonsillectomy. ConclusionsDynamic tonsillar prolapse can result in subjective exertional dyspnea and objective upper airway resistance mimicking PVFMD and treatment with adenotonsillectomy can greatly reduce symptoms.

GLI 2012 equations define few spirometric anomalies in the general population: the PneumoLaus study

BackgroundReduced lung function predicts increased mortality, but its prevalence may vary depending on definition considered, use of bronchodilation and applied reference values. We aimed to assess lung function abnormalities in Lausanne, Switzerland, and their association with clinical history.MethodsIn a general population sample, spirometry was performed and bronchodilation applied if the ratio forced expiratory volume in 1 s (FEV1) / forced vital capacity (FVC) or the FVC was below the lower limit of normal (LLN) according to Global Lung Function Initiative 2012 references. Results for FEV1/FVC according to the LLN were compared to the 0.7 fixed ratio. Respiratory risk factors, symptoms and self-reported respiratory diagnoses were recorded through a questionnaire.ResultsOut of the 3342 included subjects, 3.8% had chronic obstruction and 2.5% reversible obstruction when using the LLN; possible lung restriction alone was present in 1.8%, and associated with chronic obstruction in 0.4%. Ever smokers had a higher prevalence of abnormal spirometry, chronic obstruction and reversible obstruction; there was no difference with regard to possible restriction. Overall, chronic airway obstruction was found in 8.9% of current smokers, 4.6% of former smokers and 1.5% of never smokers. Only one third of participants with chronic obstruction were aware of a respiratory disease.ConclusionPrevalence of abnormal lung function in the population of Lausanne is low. This may be due to a low rate of ever-smokers, the application of a full bronchodilation dose, but also to inherent characteristics of this population.

Short-acting bronchodilators for the management of acute exacerbations of chronic obstructive pulmonary disease in the hospital setting: systematic review

BackgroundCurrently, there is a lack of guidelines for the use of short-acting bronchodilators (SABD) in people admitted to hospital for acute exacerbation of chronic obstructive pulmonary disease (AECOPD), despite routine use in practice and risk of cardiac adverse events.AimTo review the evidence that underpins use and optimal dose, in terms of risk versus benefit, of SABD for inpatient management of AECOPD and collate the results for future guidelines.MethodsMedline, Embase, the Cochrane Central Register of Controlled Trials, clinicaltrials.gov and International Clinical Trials Registry Platform were searched (inception to November 2017) for published and ongoing studies. Included studies were randomised controlled trials or controlled clinical trials investigating the effect of SABD (β2-agonist and/or ipratropium) on inpatients with a diagnosis of AECOPD. This review was undertaken in accordance with PRISMA guidelines and a pre-defined protocol. Due to heterogeneous methodologies, meta-analysis was not possible so the results were synthesised qualitatively.ResultsOf 1378 studies identified, 10 met inclusion criteria. Narrative synthesis of 10 studies revealed no significant differences in most outcomes of interest relative to dose, delivery via inhaler or nebuliser, and type of β2-agonist used. However, some evidence demonstrated significantly increased cardiac side effects with increased dosage of β2-agonist (45% versus 24%), P<0.05).ConclusionThis review identified a paucity of methodologically rigorous evidence evaluating use of SABD among AECOPD. The available evidence did not identify any additional benefits for participants receiving higher doses of short-acting β2-agonists compared to lower doses, or based on type of delivery method or β2-agonists used. However, there was a small increase in some adverse events for participants using higher doses of β2-agonists.

Chest tightness is relieved with the use of asthma drugs except bronchodilators

Objective: Many patients with a chief complaint of chest tightness are examined in medical facilities, and a lack of diagnosis is not uncommon. We have reported that these patients often include those with chest tightness relieved with bronchodilator use (CTRB) and those with chest tightness relieved with the use of asthma drugs except bronchodilators (CTRAEB). The purpose of this study was to demonstrate the clinical characteristics of the patients with CTRAEB and compare them with data from patients with CTRB. Methods: Patients with CTRB (n = 13) and CTRAEB (n = 7) underwent a bronchodilator test, assessments of airway responsiveness to methacholine, bronchial biopsy, and bronchial lavage under fiberoptic bronchoscopy before receiving treatment. In all, 10 healthy subjects, 11 bronchial biopsy control patients, and 10 asthmatic patients were recruited for comparison. Results: Inhalation of a short-acting ß2-agonist (SABA) increased the forced expiratory volume in one second (FEV1) by 5.1% ± 4.0% in patients with CTRB and by 1.3% ± 3.5% in patients with CTRAEB, and the difference was statistically significant (p = 0.0449). The bronchial biopsy specimens from the patients with CTRB and CTRAEB exhibited significant increases in T cells (p < .05) compared with those of the control subjects. The bronchial responsiveness to methacholine was increased in only a minor portion of patients with CTRB and CTRAEB. Conclusions: We hypothesized that the clinical condition of patients with CTRAEB involves chest tightness arising from inflammation alone, and this chest tightness is mostly associated with airway T cells, without constriction of the airways. There is little to distinguish CTRAEB from CTRB aside from the response to bronchodilator treatment.This clinical trial is registered at www.umin.ac.jp (UMIN13994, 13998, and 16741).

Évaluation de contrôle de l’asthme à Brazzaville

BackgroundIn Brazzaville, asthma is a real health public concern. Its prevalence ranges from 5.2 to 10.22% according to two surveys performed respectively in 1990 and in 2014. The aim of the present study was to evaluate asthma control in Brazzaville. Patients and methodsWe carried out an analytic descriptive, retrospective survey between 1 January 2015 and 31 December 2016 in patients hospitalized for asthma. The evaluation criteria were those of the Global Initiative for Asthma (GINA) in 2014. ResultsWe identified 83 patients hospitalized for asthma, with a prevalence about 5.71% (83/1452). Of these, 78 were included in the survey. The study population was predominantly female, with 59 cases (75.64%). The average age was 38.39 years (±16.92; range: 17–82 years). Atopy was noted in 43 cases (55.12%), with 19 cases (24.36%) of rhinitis and 24 cases (30.77%) of asthma. The average age at the time of asthma diagnosis was 14.32 years (±8.33; range: 2–37 years). Asthma was controlled in 24 cases (30.77%), partially controlled in about 40 cases (51.28%) and uncontrolled in about 14 cases (17.95%). The chief impairments seen in partially controlled and uncontrolled patients were as follows: use of short-acting bronchodilators more than twice a week in 54 cases (69.23%), nocturnal symptoms in 45 cases (57.69%), limitation of physical activities in 39 cases (50%), and diurnal symptoms occurring more than twice a week in 34 cases (43.58%). The causes of non-control were poor treatment compliance in 47 cases (60.25%), irregular follow-up in 41 cases (52.56%), self-medication in 29 cases (37.17%), and associated allergic rhinitis in 17 cases (21.79%). The cause of poor compliance was inadequate financial means in 43 cases (55.12%), and insufficient education in 34 cases (43.58%). ConclusionOur survey reveals poor control of their disease in asthmatic patients in Brazzaville. Poor treatment compliance, inadequate financial means and inadequate education about treatment were the causes of poor asthma control in this city. Strategic plans must be put in place by healthcare staff and the health authorities to improve patient awareness and enhance management of the disease.

DIFFERENTIAL DIAGNOSIS IN PEDIATRIC SEVERE ASTHMA

Introduction Despite drug treatment, a small percentage of patients with asthma cannot reach control. Therefore, it is important to have differential diagnosis in mind. Case Description Eight-year old boy diagnosed with asthma and allergic rhinitis in 2007, managed with medium dose inhaled corticosteroids, nasal steroid, and antihistamine with improvement. During the follow-up, and 4 months prior his admission, he begins with uncontrolled asthma symptoms, two short courses of systemic steroids and a high-dose inhaled steroid are indicated without improvement, no concomitant diseases are found. During the interview, he persists with uncontrolled asthma symptoms, referring persistent cough, night waking, activity limitation, and use of bronchodilator 4 to 5 times a week. On exam, he has diffused expiratory wheezing throughout all lung fields. A bronchoscopy shows a solid, 1 cm long, foreign body. Discussion The approach in patients with severe asthma is challenging to allergologists, especially when we talk about pediatric patients, where identifying the differential diagnosis is even more complicated. When the diagnosis is being hold up, the quality of life is affected in patients and their families, and the risk of developing secondary drug effects with a high-dose treatment increases. Despite drug treatment, a small percentage of patients with asthma cannot reach control. Therefore, it is important to have differential diagnosis in mind. Eight-year old boy diagnosed with asthma and allergic rhinitis in 2007, managed with medium dose inhaled corticosteroids, nasal steroid, and antihistamine with improvement. During the follow-up, and 4 months prior his admission, he begins with uncontrolled asthma symptoms, two short courses of systemic steroids and a high-dose inhaled steroid are indicated without improvement, no concomitant diseases are found. During the interview, he persists with uncontrolled asthma symptoms, referring persistent cough, night waking, activity limitation, and use of bronchodilator 4 to 5 times a week. On exam, he has diffused expiratory wheezing throughout all lung fields. A bronchoscopy shows a solid, 1 cm long, foreign body. The approach in patients with severe asthma is challenging to allergologists, especially when we talk about pediatric patients, where identifying the differential diagnosis is even more complicated. When the diagnosis is being hold up, the quality of life is affected in patients and their families, and the risk of developing secondary drug effects with a high-dose treatment increases.

Anti-IgE therapy for asthma: an audit at atertiary care centre in Saudi Arabia.

BACKGROUNDAlthough anti-IgE therapy has been shown to offer numerous benefits, we suspect it is underutilized locally. To date, there are no studies on any aspect of its use in the Arab region. There is also no information on whether physicians follow current guidelines nor on patient response to this form of therapy.OBJECTIVEAssess the use of omalizumab for patients with difficult asthma at a tertiary care center.DESIGNRetrospective, descriptive.SETTINGTertiary care hospital.PATIENTS AND METHODSInformation was collected from medical records and interviews of all patients who received a minimum of 6 months of omalizumab, including data on practices of the prescribing physician (pulmonary versus allergy), indications, dose, subjective response, number of emergency room visits and hospitalizations, changes in asthma medications, adverse effects, and the setting for delivery of therapy.MAIN OUTCOME MEASURESExtent to which current guidelines for prescribing omalizumab were followed. Patient subjective and objective responses to treatment as reflected by changes in the use of medications and lung function before and after therapy.SAMPLE SIZE50 patients.RESULTSOf the 50 consecutive patients, 35 were female and the mean (SD) age was 46.3 (9.2) years. Only 28 patients (56 %) met all the criteria for the prescription of omalizumab as per current guidelines; 18 (64%) by pulmonary and 10 (36%) by allergy physicians (P<.05). Pulmonary physicians performed more tests for conditions complicating or simulating asthma (P<.05). The mean (SD) duration of treatment by omalizumab of 35 (22) months was longer in patients managed by allergists (42 [24] months) than pulmonary physicians (30 [21] months) (P>.05). Both physician groups prescribed a lower initial dose than recommended (P<.05 recommended vs. prescribed). Patients reported a significant improvement in symptoms, reduction in the use of bronchodilators and oral steroids and in the use of healthcare services (from 16.28 [7.9] to 2.08 [1.78], P<.0001) mean values from sum of hospitalizations/year, ER visits/year, exacerbations/year, but not in other medications or pulmonary function tests (P>.05).CONCLUSIONDespite several benefits, notably a reduction in utilization of health services and asthma medication, anti-IgE therapy is probably underutilized locally. Pulmonary physicians are more likely to follow the guidelines than allergy physicians. This study suggests that there is room for improvement in the prescription practices, particularly in dosing and the setting for delivery. Further multicenter prospective studies are required to identify gaps in the current practices and improve asthma management.LIMITATIONSToo few patients met inclusion criteria, lack of control group, and use of a subjective assessment for patient symptoms as opposed to validated questionnaires.

New possibilities of pharmacotherapy for chronic obstructive pulmonary disease

The use of bronchodilators (DB) remains up to the present day the leading therapeutic strategy for the treatment of chronic obstructive pulmonary disease (COPD), in which case administration of fixed-dose combinations of long-acting bronchodilators seem the most promising. At the same time, the issues of anti-inflammatory therapy of COPD are also actively discussed, first of which is feasibility for the wide use of fixed-dose combinations of inhaled glucocorticosteroids (IHGC) with long-acting β2-agonists (LABA). Recent years are characterized by the launch of a significant number of new BDs, anti-inflammatory drugs and their combinations to the pharmaceutical market. The article considers the role and place of new drugs in the treatment of COPD having a stable course.

Decreasing Racemic Epinephrine for Bronchiolitis in an Academic Children's Hospital.

Bronchiolitis is a leading cause of pediatric hospitalizations in the United States. Although the American Academy of Pediatrics recommends against routine use of bronchodilators in bronchiolitis management, racemic epinephrine was persistently used for this purpose at Le Bonheur Children's Hospital. Our aim was to decrease racemic epinephrine use for bronchiolitis by 50% within 8 months. Our multidisciplinary team used the Institute for Healthcare Improvement's Model for Improvement to develop an aim statement, choose metrics, and perform plan-do-study-act cycles to reduce racemic epinephrine use. We used focused education through in-person and online methods and provided direct feedback to residents, respiratory therapists, and nurses primarily caring for these children. The percentage of all patients admitted for bronchiolitis receiving at least 1 dose of racemic epinephrine was collected from the medical record and recorded on statistical process control charts for distribution to their work areas. Albuterol use and length of stay were collected as balancing measures. We used statistical process control charts to establish special cause variation and identify statistically significant differences in our measures. During our intervention period, the percentage of bronchiolitis patients receiving at least 1 dose of racemic epinephrine to treat bronchiolitis decreased from an average of 26% to 5%, and similarly, albuterol use decreased from an average of 48% to 34%. There was no clinically significant difference in length of stay. Using a multidisciplinary approach and focused education techniques may be an effective way to reduce racemic epinephrine use for children with bronchiolitis.

Bronchodilator Use for Acute Chest Syndrome Among Large Pediatric Hospitals in North America.

The utility of bronchodilators to treat acute chest syndrome (ACS) in patients with sickle cell disease is unknown. Our objectives were to examine the variability in bronchodilator use for ACS among pediatric hospitals contributing to a large database and to examine the relationship between bronchodilator use and length of stay (LOS) and mortality. Between 2005 and 2011, bronchodilators were used during 6812/11 328 hospitalizations (60.1%) and use varied from 0.0% to 97.0% (median = 46.0%, interquartile range = 37.0% to 74.0%). Median LOS was 4 days, and interquartile range was 2 to 6 days. Bronchodilator use was associated with a 13.2% increase in LOS (95% confidence interval = 9.2% to 17.3%, P < .001). However, in the subgroup with asthma, bronchodilator use was associated with a 17.9% decrease in LOS (95% confidence interval = 1.7% to 31.4%, P = .03). There is wide variability in bronchodilator use for ACS, and it has variable association with LOS, depending on comorbid asthma. Prospective trials are needed to evaluate bronchodilators for ACS.

Gastroschisis and Cumulative Stressor Exposures.

Gastroschisis, a congenital defect of the abdominal wall, occurs disproportionately more in offspring of young mothers and has been increasing in prevalence over the past decades. A wide range of exposures have been reported in association with an increased gastroschisis risk, independent of mother's age; many have also been correlated with stress responses. We explored cumulative exposures to such stressor exposures among 1,261 mothers of gastroschisis cases and 10,682 mothers of controls in the National Birth Defects Prevention Study (1997-2011). We considered 16 exposures as stressors in the first trimester: fever, genitourinary infection, anti-herpetic medication use, injury, bronchodilator use, cigarette smoking, alcohol intake, illicit drug use, prescription opioid use, oral contraceptive use, interpregnancy interval < 12 months, residential move, aspirin use, ibuprofen use, venlafaxine use, and paroxetine use. Mothers of cases reported more stressor exposures than controls. For 1, 2, 3, and ≥ 4 stressor exposures compared with none, the age-adjusted odds ratios (95% confidence interval) were 1.3 (1.1, 1.6), 1.7 (1.4, 2.1), 2.5 (2.0, 3.1), and 3.6 (2.9, 4.4), respectively. When we weighted cumulative stress scores according to the magnitude of stressor-specific odds ratios, similar associations were observed. Cumulative stressor exposure did not account for the strong inverse association between age and gastroschisis risk. These findings show that gastroschisis risk appears to increase with accumulation of widely different types of exposures, consistent with the hypothesis that stress-induced inflammation might play an etiologic role.

Risk factors for chronic lung disease and asthma differ among children born extremely preterm.

To evaluate the hypothesis that chronic lung disease of prematurity (CLD) is a risk factor for asthma in children born extremely preterm, and the hypothesis that the risk factors for CLD are similar to those for asthma. A retrospective analysis was performed using data collected prospectively from 882 children born before the 28th week of gestation between 2002 and 2004 who returned for follow-up at ages 12 and 24 months and 10 years. We created time-oriented logistic regression models to compare risk factors for CLD, defined as need for supplemental oxygen at 36 weeks postmenstrual age, and parent-reported asthma at 10 years of age. CLD diagnosed during neonatal admission was associated with bronchodilator use at 12 months and 24 months (P < 0.001), but not with an asthma diagnosis at 10 years (Odds Ratio 1.3; 95% confidence interval 0.98-1.8). While risk factors for CLD include lower gestational age (OR 2.7; 1.5-4.7) and fetal growth restriction (OR 2.3; 1.4-3.7), risk factors for asthma include mother's eligibility for public insurance (Medicaid) (OR 1.8; 1.1-2.8), and higher weight gain velocity during the first year (OR 1.5; 1.02-2.2) and between the 2nd and 10th year (OR 1.7; 1.2-2.4). Among children born extremely preterm, the diagnosis of CLD and its antecedents were associated with transient preschool wheezing, but not with asthma. Post-NICU factors, such as growth velocity and socioeconomic disadvantage, appear to have stronger associations with asthma than exposures during NICU admission.

Tiotropium Withdrawal in Early-Stage Chronic Obstructive Pulmonary Disease

Background: Tiotropium improves lung function and ameliorates the annual decline in the forced expiratory volume in 1 second (FEV1) after bronchodilator use in patients with mild to moderate chronic obstructive pulmonary disease (COPD). However, whether these benefits persist in patients with early-stage COPD after tiotropium discontinuation is unknown. Methods: In this prospective cohort observational follow-up study, patients who had completed the tiotropium in early-stage COPD (Tie-COPD) trial were followed for a maximum of 3 years, continuing or discontinuing treatment according to their willingness. The outcomes measured were spirometry parameters, COPD exacerbations, COPD Assessment Test (CAT) scores, Clinical COPD Questionnaire (CCQ) scores, modified British Medical Research Council (mMRC) scores and the use of respiratory medications. Results: Of 353 patients, 262 (126 in post-placebo group and 136 in post-tiotropium group) completed the maximum 3-year follow-up after the study medication was withdrawn. After discontinuation, both the FEV1 and forced vital capacity decreased, with no significant difference between the two groups. The frequency of acute COPD exacerbations and the mMRC scores were also similar between the two groups after medication withdrawal. Both the mean CAT and CCQ scores were significantly lower in the post-tiotropium group than in the post-placebo group (P<0.05 for all comparisons) at the 1-year follow-up after withdrawal, but they were not different at the next follow-up. Conclusion: Tiotropium should be continued because the lung function of the patients who had received regular treatment with tiotropium began to decline after tiotropium was withdrawn. Funding: Supported by grants from the National Key Technology Research and Development Program of the 12th and 13th National 5-Year Development Plan (2012BAI05B01 and 2016YFC1304100). Declaration of Interest: No potential conflict of interest relevant to this article was reported. Ethical Approval: The trial protocol was approved by the local institutional review board or independent ethics committee at each site according to the requirement of the Chinese guidelines for Good Clinical Practice. All participants provided written informed consent before enrollment.

Short-term benefit of smoking cessation along with glycopirronium on lung function and respiratory symptoms in mild COPD patients: a retrospective study

Introduction. Tobacco smoke is the leading cause of chronic obstructive pulmonary disease (COPD). Smoking cessation can change the natural history of COPD, as we know from the GOLD guidelines. Little is known about the short-term clinical and functional effects of smoking cessation treatment combined with anti-muscarinic bronchodilators. Objective. To determine whether quitting smoking, obtained by smoking cessation treatment combined with the use of a new long-acting muscarinic antagonist bronchodilator (LAMA), can improve lung function tests and respiratory symptoms more than the use of LAMA alone. Methods. We evaluated, in a retrospective analysis, the functional and clinical data, collected in one year, of 120 patients who were current smokers affected by mild COPD and who quit smoking using smoking cessation treatment combined with glycopirronium. We compared them with a group of 80 patients with mild COPD undergoing the same treatment but who did not quit smoking. All patients underwent functional and clinical tests at baseline and at a third-month check. Measurements and main results. The two groups were homogeneous in terms of demographic data without significant differences. All patients used varenicline for smoking cessation. They all performed the following tests: a spirometry with detection of resistances, the 6 min walking test, haemogasanalysis, the exhaled CO test, the COPD assessment test (CAT) and finally the modified Medical Research Council test (mMRC). A significant improvement in the functional tests at the third-month check was found in both groups—quitters and non-quitters. However, a notable increase in the examined parameters was registered in the group of patients who quit smoking, in particular, we observed a significant increase at the third-month check of the parameter forced expiratory volume in 1 s (FEV1) of more than 200 ml with p < 0.001. A comparison between quitters and non-quitters revealed a major benefit derived from smoking cessation in terms of functional changes and symptom relief. In particular, not only FEV1 but also forced expiratory flow at 25%–75% of vital capacity (FEF 25–75) (p < 0.01) and CAT (p < 0.001) were found to be significantly improved in patients who quit than in patients who did not at the check time point. Conclusions. Smoking cessation treatment obtained by varenicline was confirmed as a crucial therapeutic option, especially when combined with bronchodilator in mild COPD. Patients who quit smoking could already benefit from both treatments in the short term, improving lung function and respiratory symptoms and therefore improving their quality of life.