Increased Airflow Obstruction Research Articles

Role of exosomes in exacerbations of asthma and COPD: a systematic review.

Asthma and chronic obstructive pulmonary disease are chronic respiratory disorders characterized by airways obstruction and chronic inflammation. Exacerbations lead to worsening of symptoms and increased airflow obstruction in both airways diseases, and they are associated with increase in local and systemic inflammation. Exosomes are cell-derived membrane vesicles containing proteins, lipids, and nucleic acids that reflect their cellular origin. Through the transfer of these molecules, exosomes act as mediators of intercellular communication. Via selective delivery of their contents to target cells, exosomes have been proved to be involved in regulation of immunity and inflammation. Although, exosomes have been extensively investigated in different diseases, little is currently known about their role in asthma and COPD pathogenesis, and particularly in exacerbations. This review aims to systemically assess the potential role of exosomes in asthma and COPD exacerbations.

Physical activity and outcomes in Japanese patients with chronic obstructive pulmonary disease: From the Ishinomaki COPD Network registry

BackgroundLow physical activity levels are associated with an increased risk of exacerbations and all-cause mortality in patients with chronic obstructive pulmonary disease (COPD); however, evidence is limited in a population with a low frequency of exacerbations, such as the Japanese population. This study investigated the effects of physical activity on outcomes in Japanese patients with COPD. MethodsWe conducted a prospective observational study in a cohort of Japanese patients with COPD between April 2018 and July 2020. Characteristics, frequency of exacerbations, and mortality were assessed during the 1-year follow-up period. Logistic regression analysis evaluated the relationship between physical activity and outcomes. ResultsA total of 309 patients (294 males; median age, 75 years) with stable COPD were included, and 307 completed follow-up. Patients with lower levels of physical activity were older, and showed increased airflow obstruction, limited exercise capacity, increased dyspnea, depressive state, poor health status, muscle weakness, and more information needs for the disease. Patients with high levels of physical activity had a lower risk of exacerbation, including hospital admission, compared to those with low levels of activity (odds ratio [OR], 0.46; 95 % confidence interval [CI], 0.22–0.97; and OR, 0.21; 95 % CI, 0.09–0.50, respectively). High physical activity was associated with a reduced risk of all-cause mortality (OR, 0.07; 95 % CI, 0.01–0.55) and respiratory mortality (OR, 0.16; 95 % CI, 0.02–1.47). ConclusionsThese findings showed that higher physical activity is associated with better clinical outcomes, even in a COPD population with a low frequency of exacerbations.

Interaction effect of chronic cough and ageing on increased risk of exacerbation in patients with asthma: a prospective cohort study in a real-world setting.

Older adults with asthma have the greatest burden and worst outcomes, and there is increasing evidence that chronic cough (CC) is associated with asthma severity and poor prognosis. However, the clinical characteristics of older adult patients with both asthma and CC remain largely unknown. Participants with stable asthma underwent two cough assessments within 3 months to define the presence of CC. Patients were divided into four groups based on CC and age (cut-off ≥60 years). Multidimensional assessment was performed at baseline, followed by a 12-month follow-up to investigate asthma exacerbations. Logistic regression models were used to explore the interaction effect of CC and age on asthma control and exacerbations. In total, 310 adult patients were prospectively recruited and divided into four groups: older CC group (n=46), older non-CC group (n=20), younger CC group (n=112) and younger non-CC group (n=132). Compared with the younger non-CC group, the older CC group had worse asthma control and quality of life and increased airflow obstruction. The older CC group showed an increase in moderate-to-severe exacerbations during the 12-month follow-up. There was a significant interaction effect of CC and ageing on the increased moderate-to-severe exacerbations (adjusted risk ratio 2.36, 95% CI 1.47-3.30). Older asthma patients with CC have worse clinical outcomes, including worse asthma control and quality of life, increased airway obstruction and more frequent moderate-to-severe exacerbations, which can be partly explained by the interaction between CC and ageing.

Cardiovascular and Pulmonary Responses to Acute Use of Electronic Nicotine Delivery Systems and Combustible Cigarettes in Long-Term Users

The acute cardiovascular and pulmonary effects of contemporary electronic nicotine delivery systems (ENDS) in long-term users are not known. What are the cardiovascular and pulmonary responses to an acute 15-min product use challenge with ENDS and combustible cigarettes in regular nicotine-containing product users compared with control participants who do not use tobacco or vape? Observational challenge study before and after nicotine-containing product use of 395 individuals who used ENDS exclusively (n= 164; exhaled carbon monoxide level,< 5 parts per million [ppm]; positive urine NicCheck I [Mossman Associates] results, 82%; fourth-generation ENDS), participants who smoked cigarettes exclusively (n= 117; carbon monoxide level, > 5 ppm; positive urine NicCheck I results), and control participants (n= 114; carbon monoxide level,< 5 ppm; negative urine NicCheck I results). During the 15-min product challenge, cigarette users took a median of 14.0 puffs (interquartile range [IQR], 9.3 puffs); ENDS users took 9.0 puffs (IQR, 7.5 puffs; P< .001). After product challenge, compared with control participants, ENDS users showed greater increases in adjusted mean differences in systolic BP (5.6mmHg [95%CI, 4.4-6.8mmHg] vs2.3mmHg [95%CI, 0.8-3.8mmHg]; P= .001), diastolic BP (4.2mmHg [95%CI, 3.3-5.0mmHg] vs2.0mmHg [95%CI, 1.1-3.0mmHg; P= .003), and heart rate (4.8 beats/min [95%CI, 4.0-5.6 beats/min] vs-1.3 beats/min [95%CI, -2.2 to -0.3 beats/min]; P< .001) and greater reductions in brachial artery diameter (-0.011cm [95%CI, -0.013 to 0.009cm] vs-0.006cm [95%CI, -0.004 to -0.009cm]; P= .003), time-domain heart rate variability (-7.2 ms [95%CI, -10.5 to -3.7 ms] vs3.6 ms [95%CI, 1.6-9.3 ms]; P= .001), and FEV1 (ENDS: -4.1 [95%CI, -5.4 to -2.8] vscontrol participants: -1.1 [95%CI, -2.7 to 0.6]; P= .005) with values similar to those of cigarette users. ENDS users performed worse than control participants on all exercise parameters, notably metabolic equivalents (METs; adjusted mean difference, 1.28 METs [95%CI, 0.73-1.83 METs]; P< .001) and 60-s heart rate recovery (adjusted mean difference, 2.9 beats/min [95%CI, 0.7-5.0 beats/min]; P= .008). ENDS users had acute worsening of blood pressure, heart rate, and heart rate variability, as well as vasoconstriction, impaired exercise tolerance, and increased airflow obstruction after vaping, compared to control participants. ClinicalTrials.gov; No.: NCT03863509; URL: www. gov.

Chronic Lung Allograft Dysfunction with Expiratory Flow Limitation: A Novel Sub-Phenotype Associated with Increasing Small Airway Resistance and CLAD Severity

<h3>Purpose</h3> Expiratory flow limitation (EFL) during tidal breathing is a major determinant of dynamic hyperinflation, dyspnoea and exercise limitation in obstructive lung disease. Within breath respiratory system reactance, measured by oscillometry, accurately detects EFL. The aim of this study is to assess predictors of EFL in recipients with chronic lung allograft dysfunction (CLAD). <h3>Methods</h3> A cross-sectional study was performed on bilateral lung transplant (LTx) recipients with persistent lung allograft dysfunction at 2 Australian centres between Jan-20 and Jun-21. Spirometry and oscillometry (TremoFlo C-100) were performed to obtain FEV₁, FVC and X_rs at 5Hz, R_5-19 respectively. EFL was defined as [mean inspiratory - mean expiratory X_rs (∆Xrs)] > 2.53. Patients with CLAD, based on 2019 Consensus criteria and phenotyping, were included. Recipients with non-CLAD causes of lung allograft dysfunction were excluded. Logistic regression measured the association between demographic and physiologic predictors and risk of EFL. <h3>Results</h3> A total of 110 bilateral lung transplant recipients with persistent lung allograft dysfunction were enrolled. 20 patients were excluded and 90 with confirmed CLAD were included for final analysis. EFL was observed in 16 (17.8%) patients. The median (IQR) ∆Xrs in recipients with EFL was 3.40 (2.10) compared to -0.14 (1.37) in those without. In univariable analysis, reduced concurrent FEV₁/FVC (OR 0.01 95%CI 0.00-0.43, p=0.018), reduced concurrent FEV₁ as %-baseline (OR 0.02 95%CI 0.00-0.72, p=0.03) and increased R_5-19 Z-Score (OR 1.30 95%CI 1.11-1.52, p=0.001) were associated with an increased risk of EFL. Recipient BMI (OR 1.07 95%CI 0.99-1.16, p=0.09) was positively correlated with EFL with a weak association. CLAD BOS phenotype (BOS OR 0.82 95%CI 0.25-2.64, p=0.73) was not associated with an increased risk of EFL compared to other phenotypes. <h3>Conclusion</h3> EFL occurs in a minority of patients with CLAD, and occurs both in BOS and non-BOS phenotypes. Increasing airflow obstruction, CLAD severity and small airway resistance (R_5-19) are associated with an increased risk of EFL. Advanced fibroproliferative small airway obstruction likely explains these associations. CLAD with EFL may be associated with poor outcomes and routine monitoring with oscillometry may be beneficial.

Clinical and inflammatory characteristics of patients with asthma in the Spanish MEGA project cohort.

IntroductionThe MEGA (MEchanism underlying the Genesis and evolution of Asthma) project is a multicenter cohort study carried out in eight Spanish hospitals, gathering clinical, physiological, and molecular data from patients with asthma and multimorbidities in order to gain insight into the different physiopathological mechanisms involved in this disorder.Material and MethodsWe report the baseline clinical and physiological characteristics and biomarker measures of adult participants in the project with the aim of better understanding the natural history and underlying mechanisms of asthma as well as the associated multimorbidities across different levels of severity. We carried out a detailed clinical examination, pulmonary function testing, measurement of fractional exhaled nitric oxide (FeNO), blood counts, induced sputum, skin prick tests, chest computed tomography scan, asthma questionnaires, and multimorbidity assessment in 512 asthmatic patients.ResultsWhen compared to patients with milder disease, severe asthmatic patients showed greater presence of symptoms, more exacerbations, lower asthma control, increased airflow obstruction, and higher frequency of chronic rhinosinusitis with nasal polyps, severe rhinitis, anxiety and depression, gastroesophageal reflux, and bronchiectasis.ConclusionThe MEGA project succeeded in recruiting a high number of asthma patients, especially those with severe disease, who showed lower control and higher frequency of multimorbidities.

Nitrogen dioxide exposure in school classrooms of inner-city children with asthma

Ambient and home exposure to nitrogen dioxide (NO2) causes asthma symptoms and decreased lung function in children with asthma. Little is known about the health effects of school classroom pollution exposure. We aimed to determine the effect of indoor classroom NO2 on lung function and symptoms in inner-city school children with asthma. Children enrolled in the School Inner-City Asthma Study were followed for 1 academic year. Subjects performed spirometry and had fraction of exhaled nitric oxide values measured twice during the school year at school. Classroom NO2 was collected by means of passive sampling for 1-week periods twice per year, coinciding with lung function testing. Generalized estimating equation models assessed lung function and symptom relationships with the temporally nearest classroom NO2 level. The mean NO2 value was 11.1ppb (range, 4.3-29.7ppb). In total, exposure data were available for 296 subjects, 188 of whom had complete spirometric data. At greater than a threshold of 8ppb of NO2 and after adjusting for race and season (spirometry standardized by age, height, and sex), NO2 levels were associated highly with airflow obstruction, such that each 10-ppb increase in NO2 level was associated with a 5% decrease in FEV1/forced vital capacity ratio (β=-0.05; 95% CI, -0.08 to -0.02; P=.01). Percent predicted forced expiratory flow between the 25th and 75th percentile of forced vital capacity was also inversely associated with higher NO2 exposure (β=-22.8; 95% CI, -36.0 to -9.7; P=.01). There was no significant association of NO2 levels with percent predicted FEV1, fraction of exhaled nitric oxide, or asthma symptoms. Additionally, there was no effect modification of atopy on lung function or symptom outcomes. In children with asthma, indoor classroom NO2 levels can be associated with increased airflow obstruction.

Alternative Macrophage Activation Is Increased in Asthma.

The immune responses of type 2 T helper cells (Th2) play an important role in asthma and promote the differentiation of alternatively activated (M2) macrophages. M2 macrophages have been increasingly understood to contribute to Th2 immunity. We hypothesized that M2 macrophages are altered in asthma and modulate Th2 responses. The aim of this study was to characterize the phenotype and function of human monocyte-derived M2 and bronchoalveolar lavage fluid (BALF) macrophages from healthy control subjects and subjects with asthma. Phenotypic characteristics and effector function of M2 macrophages were examined using monocyte-derived and BALF macrophages obtained from subjects with asthma (n = 28) and healthy volunteers (n = 9) by flow cytometry and quantitative PCR. Resting monocyte-derived (M0) and M2 macrophages were generated by the addition of macrophage colony-stimulating factor or macrophage colony-stimulating factor plus IL-4, respectively. M2 macrophage cytokine expression and their impact on dendritic and CD4+ T cell activation were examined in vitro. High levels of CD206 and major histocompatibility complex class II expression identify macrophages with an M2 phenotype that are increased 2.9-fold in the BALF of subjects with asthma compared with control subjects. M2 macrophages have elevated IL-6, IL-10, and IL-12p40 production compared with conventional macrophages and modulate dendritic and CD4+ T cell interactions. Histamine receptor 1 and E-cadherin expression identify M2 macrophage subsets associated with increased airflow obstruction. M2 macrophages have a distinct cell surface and effector phenotype and are found in increased numbers in subjects with asthma. These findings suggest that M2 macrophages may play an important role in allergic asthma through their bidirectional interactions with immune and structural cells, and inflammatory mediators.

P126 Breathlessness And Lung Function Predicts Future Work Disability In Older Workers: Detection, Intervention, Retention?

Economic pressures and the ageing population have increased the importance of maintaining fitness to work in older adults. Dyspnoea and airflow limitation are associated with disability particularly in individuals with diagnosed disease. A cross-sectional general population survey of 51–60 year olds demonstrated significant associations between breathlessness, airflow obstruction and work performance; a follow-up survey was completed 18 months later to examine changes in work. Participants from the first study were sent a postal questionnaire asking about job and employment changes. Questionnaire and spirometry results from the initial study were used to define breathlessness (modified MRC scale) and airflow obstruction (GOLD stage) respectively. Information from the follow up questionnaire was also used to identify cases, defined as those who had experienced a change in employment, and frequency matched controls of the same gender, who reported no change in work circumstances (with a ratio of two controls per case). Results from respondents to the follow up questionnaire (1663/1773 (94%)), all of whom had been in full time work at the time of the first study) showed that the majority (78.5%) continued in full time employment; however 10.6% were working part time and 10.9% were no longer in paid employment at follow up. Of the participants still in employment who reported changing their hours or activity at work, 9.3% stated that this change had been to their health. Prevalence of economic inactivity rose with increasing breathlessness and with increasing airflow obstruction in workers of both sexes; these relationships were statistically significant in all cases except for airflow obstruction in women (Figure). The odds of GOLD stage 1 or greater airflow obstruction was significantly higher in cases than in controls (unadjusted OR 1.71, 95% CI 1.10–2.77, p = 0.02). These findings suggest that breathlessness and airflow obstruction are associated with subsequent job instability and premature loss from the workforce in older workers. A focused surveillance programme could identify those at higher risk of employment problems with the intention of ameliorating them – providing that there are suitable interventions available to support continuing workforce activity in adults in their sixth decade of life and beyond.

78 * IS GRIP STRENGTH ASSOCIATED WITH LUNG FUNCTION IN OLDER HOSPITALISED PATIENTS?

Introduction: Age-related airway compliance changes contribute to the declining ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) with ageing. This leads to increased airflow obstruction during forced expiration. Consequently, many older people meet the spirometric criteria for obstructive airways disease despite no other evidence. Older people may be unable to generate and sustain sufficient expiratory pressure to reach and hold maximum flow as lung volume falls. This study used grip strength (GS) to reflect expiratory muscle strength (EMS) in investigating the relationship between EMS and lung function (LF). Methods: Patients on acute Medicine for Older People wards were recruited who met the inclusion criteria: age above 70 years; never smoked; no history, symptoms or signs of respiratory disease; Mini Mental State Examination (MMSE) ≥24; willing and able to consent to participate; able to perform hand grip and forced spirometry. Outcome measure was LF (FEV1, FVC, FEV1/FVC, peak expiratory flow rate (PEFR) and slow vital capacity (SVC)), covariates were GS, age, weight, height. Unadjusted and adjusted (for age, height, weight) linear regressions were used for analysis. Results: 50 patients (male = 20, female = 30) were recruited. Significant relationships were found in men between GS and FEV1 (unadjusted β = 0.032, 95%CI = (0.001,0.063), p = 0.047) although not significant after adjustment; in women between GS and PEFR (unadjusted β = 6.881, 95%CI = 1.537,12.226, p = 0.013); (adjusted β = 6.938, 95%CI = 1.268,12.607, p = 0.018), and in women between GS and SVC (unadjusted β = 0.052, 95%CI = 0.006,0.099, p = 0.028); (adjusted β = 0.050, 95%CI = 0.0005,0.100, p = 0.048). No other significant relationship was found. Conclusions: The relationship of GS with PEFR and SVC in women might reflect stronger patients generating higher intra-thoracic pressure at the start of spirometry and pushing harder against thoracic cage recoil at end-expiration. No significant relationship was found with FEV1/FVC and GS in this small study. Further research is needed to evaluate the relationship between LF and GS.

Integrating Evidence for Managing Asthma in Patients Who Smoke

Cigarette smoking among asthma patients is associated with worsening symptoms and accelerated decline in lung function. Smoking asthma is also characterized by increased levels of neutrophils and macrophages, and greater small airway remodeling, resulting in increased airflow obstruction and impaired response to corticosteroid therapy. As a result, smokers are typically excluded from asthma randomized controlled trials (RCTs). The strict inclusion/exclusion criteria used by asthma RCTs limits the extent to which their findings can be extrapolated to the routine care asthma population and to reflect the likely effectiveness of therapies in subgroups of particular clinical interest, such as smoking asthmatics. The inclusion of smokers in observational asthma studies and pragmatic trials in asthma provides a way of assessing the relative effectiveness of different treatment options for the management of this interesting clinical subgroup. Exploratory studies of possible treatment options for smoking asthma suggest potential utility in: prescribing higher-dose ICS; targeting the small airways of the lungs with extra-fine particle ICS formulations; targeting leukotreines, and possibly also combinations of these options. However, further studies are required. With the paucity of RCT data available, complementary streams of evidence (those from RCTs, pragmatic trials and observational studies) need to be combined to help guide judicious prescribing decisions in smokers with asthma.

Effects of feedback on the perception of inspiratory resistance in children with persistent asthma: a signal detection approach.

Accurate perception of asthma episodes increases the likelihood that they will be managed effectively. The purpose of the study was to examine the effect of feedback in a signal detection task on perception of increased airflow obstruction in children with persistent asthma. The effect of feedback training on the perception of resistive loads was evaluated in 155 children with persistent asthma between 8 and 15 years of age. Each child participated in four experimental sessions that occurred approximately once every 2 weeks, an initial session followed by three training sessions. During the initial session, the threshold resistance to breathing was determined for each child. Subsequently, each child was randomly assigned to one of two resistive load training conditions in a signal detection paradigm: training with immediate performance feedback or training with no performance feedback. The threshold resistance to breathing, determined in the initial session, was equivalent between groups. Children in the feedback condition discriminated more accurately between both the presence and the absence of increases in the resistance to breathing (206 [48] versus 180 [39] correct responses, p < .001), and differences over time between groups increased reliably as a function of training (165 [40] versus 145 [32] correct responses, p < .001). Response times and confidence ratings were equivalent between groups, and no differences in breathing patterns were observed between conditions. Feedback training results in improved perception of respiratory sensations in children with asthma, a finding with implications for strategies of asthma self-management.

DHEA-S inhibits human neutrophil and human airway smooth muscle migration

Airway diseases such as asthma, emphysema, and chronic bronchitis are, in part, characterized by reversible airflow obstruction and inflammation. In severe disease, marked decreases in lung function are associated with airway smooth muscle proliferation and airway neutrophilia. Inhaled glucocorticoids attenuate increased airflow obstruction and airway inflammation that occur, in part, due to increased smooth muscle migration and proliferation, as well as the airway neutrophilia. Glucocorticoids, however, have adverse side effects and, in some patients, are ineffective despite high doses. Recent research has explored the effects of non-traditional steroids on attenuation of inflammation associated with airway diseases. These non-traditional steroids have improved side effect profiles in comparison to glucocorticoid therapy. Our studies assessed effects of dehydroepiandrosterone-3-sulfate (DHEA-S) on migration of both human peripheral blood neutrophils (PMN) and human airway smooth muscle cells (HASM). DHEA-S dose-dependently inhibited chemotaxis of PMN and HASM while having no effect on the phosphorylation levels of Akt, ERK1/2, p38 MAPK or PKC, canonical positive regulators of cell migration. These studies demonstrate direct effects of DHEA-S on cell migration, thereby suggesting that DHEA-S may attenuate airway inflammation and cell migration.

Dynamic Hyperinflation During Daily Activities: Does COPD Global Initiative for Chronic Obstructive Lung Disease Stage Matter?

One of the contributors to exercise limitation in COPD is dynamic hyperinflation. Although dynamic hyperinflation appears to occur during several exercise protocols in COPD and seems to increase with increasing disease severity, it is unknown whether dynamic hyperinflation occurs at different severity stages according to the Global initiative for chronic Obstructive Lung Disease (GOLD) in daily life. The present study, therefore, aimed to compare dynamic hyperinflation between COPD GOLD stages II-IV during daily activities.Thirty-two clinically stable patients with COPD GOLD II (n = 10), III (n = 12), and IV (n = 10) participated in this study. Respiratory physiology during a daily activity was measured at patients' homes with Oxycon Mobile. Inspiratory capacity maneuvers were performed at rest, at 2-min intervals during the activity, and at the end of the activity. Change in inspiratory capacity is commonly used to reflect change in end-expiratory lung volume (DeltaEELV) and, therefore, dynamic hyperinflation. The combination of static and dynamic hyperinflation was reflected by inspiratory reserve volume (IRV) during the activity.Overall, increase in EELV occurred in GOLD II-IV without significant difference between the groups. There was a tendency for a smaller DeltaEELV in GOLD IV. DeltaEELV was inversely related to static hyperinflation. IRV during the daily activity was related to the level of airflow obstruction.Dynamic hyperinflation occurs independent of GOLD stage during real-life daily activities. The combination of static and dynamic hyperinflation, however, increases with increasing airflow obstruction.

Anti-inflammatory Treatment after Discharge Home from the Emergency Department in Adults with Acute Asthma

Airway inflammation from respiratory infections or exposure to allergens, irritants, or both leads to increased airflow obstruction and respiratory symptoms in patients with acute asthma. Antiinflammatory therapy with systemic corticosteroids (CSs) is therefore a cornerstone of the management of patients with acute asthma, particularly those presenting to the emergency department (ED) (1, 2). After initial management in the ED, most patients improve sufficiently to be discharged home with instructions to complete a short course of daily oral corticosteroids (OCSs) and short-acting inhaled bronchodilators as needed for symptom relief. Unfortunately, up to one third of patients who initially respond to therapy relapse within the first 3 to 4 weeks after ED discharge (e.g., require treatment escalation, urgent care or ED visits, or hospitalizations for asthma) (3, 4). The propensity of many patients to relapse after ED discharge has led to a number of randomized clinical trials evaluating alternative outpatient antiinflammatory treatment strategies in this population, including the use of inhaled corticosteroids (ICSs), intramuscular corticosteroids (IMCSs), and noncorticosteroid anti-inflammatory regimens. The objective of this systematic review is to synthesize the results of randomized clinical trials in adults with acute asthma, comparing alternative outpatient anti-inflammatory treatment strategies to reduce the risk of relapse after discharge home from the ED. More specifically, this systematic review examined the following anti-inflammatory treatment options in adults after ED discharge: (1) IMCSs versus OCSs, (2) ICSs versus OCSs, (3) combination of ICSs plus OCSs versus OCSs alone, and (4) noncorticosteroid anti-inflammatory agents (macrolide antibiotics and leukotriene modifiers) in addition to systemic corticosteroids. This report updates previously published systematic reviews in acute asthma (5–7) with subsequently published studies and provides a single document summarizing this body of literature for easy use by clinicians.

Anti-Inflammatory Treatment After Discharge Home from the Emergency Department in Adults with Acute Asthma

Airway inflammation from respiratory infections or exposure to allergens, irritants, or both leads to increased airflow obstruction and respiratory symptoms in patients with acute asthma. Antiinflammatory therapy with systemic corticosteroids (CSs) is therefore a cornerstone of the management of patients with acute asthma, particularly those presenting to the emergency department (ED) (1, 2). After initial management in the ED, most patients improve sufficiently to be discharged home with instructions to complete a short course of daily oral corticosteroids (OCSs) and short-acting inhaled bronchodilators as needed for symptom relief. Unfortunately, up to one third of patients who initially respond to therapy relapse within the first 3 to 4 weeks after ED discharge (e.g., require treatment escalation, urgent care or ED visits, or hospitalizations for asthma) (3, 4). The propensity of many patients to relapse after ED discharge has led to a number of randomized clinical trials evaluating alternative outpatient antiinflammatory treatment strategies in this population, including the use of inhaled corticosteroids (ICSs), intramuscular corticosteroids (IMCSs), and noncorticosteroid anti-inflammatory regimens. The objective of this systematic review is to synthesize the results of randomized clinical trials in adults with acute asthma, comparing alternative outpatient anti-inflammatory treatment strategies to reduce the risk of relapse after discharge home from the ED. More specifically, this systematic review examined the following anti-inflammatory treatment options in adults after ED discharge: (1) IMCSs versus OCSs, (2) ICSs versus OCSs, (3) combination of ICSs plus OCSs versus OCSs alone, and (4) noncorticosteroid anti-inflammatory agents (macrolide antibiotics and leukotriene modifiers) in addition to systemic corticosteroids. This report updates previously published systematic reviews in acute asthma (5–7) with subsequently published studies and provides a single document summarizing this body of literature for easy use by clinicians.

Anti-inflammatory treatment after discharge home from the emergency department in adults with acute asthma

Airway inflammation from respiratory infections or exposure to allergens, irritants, or both leads to increased airflow obstruction and respiratory symptoms in patients with acute asthma. Antiinflammatory therapy with systemic corticosteroids (CSs) is therefore a cornerstone of the management of patients with acute asthma, particularly those presenting to the emergency department (ED) (1, 2). After initial management in the ED, most patients improve sufficiently to be discharged home with instructions to complete a short course of daily oral corticosteroids (OCSs) and short-acting inhaled bronchodilators as needed for symptom relief. Unfortunately, up to one third of patients who initially respond to therapy relapse within the first 3 to 4 weeks after ED discharge (e.g., require treatment escalation, urgent care or ED visits, or hospitalizations for asthma) (3, 4). The propensity of many patients to relapse after ED discharge has led to a number of randomized clinical trials evaluating alternative outpatient antiinflammatory treatment strategies in this population, including the use of inhaled corticosteroids (ICSs), intramuscular corticosteroids (IMCSs), and noncorticosteroid anti-inflammatory regimens. The objective of this systematic review is to synthesize the results of randomized clinical trials in adults with acute asthma, comparing alternative outpatient anti-inflammatory treatment strategies to reduce the risk of relapse after discharge home from the ED. More specifically, this systematic review examined the following anti-inflammatory treatment options in adults after ED discharge: (1) IMCSs versus OCSs, (2) ICSs versus OCSs, (3) combination of ICSs plus OCSs versus OCSs alone, and (4) noncorticosteroid anti-inflammatory agents (macrolide antibiotics and leukotriene modifiers) in addition to systemic corticosteroids. This report updates previously published systematic reviews in acute asthma (5–7) with subsequently published studies and provides a single document summarizing this body of literature for easy use by clinicians.

Elevated TNFα production in whole blood in patients with severe COPD: the potential link to disease severity

The relationship between tumour necrosis factor-alpha (TNFalpha), severity of pulmonary disease and nutritional depletion in chronic obstructive pulmonary disease (COPD) remains unclear. We aimed to clarify the role of lipopolysaccharide (LPS) as a potential stimulus of cytokine production and the role of these cytokines in the alteration of body composition in patients with different degrees of COPD. We studied 29 weight-stable out-patients with different severites of COPD who had no evidence of recent infection or significant co-morbidity. Baseline serum TNFalpha levels and TNFalpha response to LPS in whole blood were measured in patients and 20 aged matched controls. Serum TNFalpha was significantly elevated in patients versus controls (2.1 +/- 0.3 vs. 1.1 +/- 0.1 pg/ml, mean +/- SEM, P = 0.007). In patients with COPD, we found a significant correlation between serum TNFalpha levels and disease severity, assessed as FEV(1) %predicted (r = 0.49, P = 0.02). Response to lipopolysaccharide did not differ significantly between patients and controls. However, within the patient group those with more severe disease (FEV(1) < or = 30% predicted, n = 12) had an enhanced response compared to patients with mild-to-moderate disease (all P < 0.05 for LPS > 1 ng/ml). Spontaneous TNFalpha production was 5.0 times higher in patients with severe COPD compared to mild-to-moderate COPD (P = 0.02). There was no relation between body composition and serum TNFalpha or TNFalpha response to LPS. Increasing airflow obstruction and hypercapnia are associated with an enhanced TNFalpha response in COPD.

No Difference in Asthma Control Among Obese Children Despite Increased Airflow Obstruction Compared to Non-obese Children

RATIONALE: Complex interactions regarding pathophysiologic relations between pediatric asthma and obesity have been reported. We evaluated effects of obesity on pediatric asthma control using the asthma control test (ACT), pulmonary function, and physician asthma control assessment (controlled, uncontrolled, or poorly controlled) based on the 2007 NAEPP guidelines. METHODS: Retrospective chart reviews were performed on 157 randomly selected patients ages 6-21 years selected from our clinic population. Data collection from the most recent visit included age, sex, race, body mass index (BMI) percentile for age, ACT score, FEV1, FEV1/FVC ratio, FEF25-75 and physician assessment of asthma control. RESULTS: There were 134 complete data sets that compared obese (defined as BMI percentile ≥ 95, n = 54) versus non-obese patients. There were no significant group differences in sex, race or mean ACT scores. In the obese group, mean FEV1 was 92% and mean FEF25-75 was 85% predicted compared to 93% and 88% (respectively) in the non-obese groups. FEV1/FVC was 83% in the obese vs. 91% in the non-obese groups (p < 0.05). There were no significant group differences in physician assessment. CONCLUSIONS: Obese children with asthma appear to have increased airflow obstruction compared to their non-obese counterparts not reflected in either ACT scores or physician asthma control assessment, emphasizing the limitations of current asthma assessment methods, and questioning the clinical value of isolated subjective perceptions of asthma control. Obese patients may be at risk for more severe disease due to non-perceived factors. Further work is needed to identify these factors.

MMP-9 protein level does not reflect overall MMP activity in the airways of patients with COPD

Animal and human studies have implicated an imbalance of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in the pathogenesis of chronic obstructive pulmonary disease (COPD). MMP-9 protein is increased in COPD and we hypothesized that total MMP activity would be raised although this has not previously been measured. Using fluorescence and biotin labelled MMP assays, RT-PCR, western blotting and enzyme-linked immunosorbent assay we examined total MMP activity, specific gelatinase, elastase, collagenase activity, TIMP-1 and TIMP-2 in induced sputum from smokers with COPD and smokers without COPD. Induced sputum was obtained from 15 smokers with COPD and 14 smokers without COPD. MMP-9 levels were higher in those with COPD compared with controls (p<0.05). Total MMP activity, specific gelatinase, collagenase and elastase activities were not higher in COPD patients. In addition, reduced MMP activity was correlated with increasing airflow obstruction in COPD (p=0.016). MMP-9 protein but not MMP activity was higher in sputum of COPD patients compared with controls. These results suggest that MMP-9 levels may not reflect the overall MMP activity in the airways of patients with COPD suggesting a complex relationship between MMP-9 protein and activity. Further studies of MMPs in COPD should comprise activity measures in addition to protein levels.